Further, 31 emphasizes the inverse atom population with respect to the ubiquitous Fe 3 S 4 core found in the medial cluster of the [NiFe]-hydrogenase electron transfer chain and elsewhere. Reaction [ 9 ] is currently the only desulfurization reaction leading to isolable Fe 4 S 3 clusters. Individual cubane units can be covalently coupled to each other to form higher nuclearity cores. Clusters containing the cores 34 and 35 are prepared as phosphine clusters, although the former has also been isolated in carbene-ligated form as 12 Figure 3.
In solution, these clusters can be equilibrated with each other in the presence of added phosphine. While other high-nuclearity clusters are known, 28 only those with cores are constructed of discrete cubane units, raising the possibility that they may also be found in proteins. Several other clusters built from cubane or cuboidal units can be recognized 81 but are hypothetical in the iron-sulfur context.
Lastly, the EBDC core is emphasized here because of the role of this structure type in the synthesis of higher nuclearity heterometal clusters cf. The vertices of cubane-type clusters can be differentiated in ways other than by alteration of terminal ligands. The most prominent, longstanding case continues the 3: These can be considered substituted versions of all-iron Although MFe 3 S 4 cores depart from the familiar and efficient idealized symmetry of the Fe 4 S 4 cubane structure, the heterometallic cores naturally conform to the homometallic parent structures via the common Fe 3 S 4 fragment.
The attributes of these heterometal clusters parallel those of Fe 4 S 4 clusters and include multiple oxidation states, similar overall cubane geometries with metric differences confined mainly to the heterometal environment, and substitutional lability at the tetrahedral iron sites involving thiolate and pseudo halide binding in particular. Schematic depiction of homometal and heterometal cluster cores and the synthesis of heterometal cores by fragment condensation reaction [8]. The history of biological heterometallic M-Fe-S clusters extends back to several key events.
These include the partial structure determination of the Mo-Fe-S cluster of the nitrogenase cofactor, 82 recognition of the voided Fe 3 S 4 motif in proteins, 83 , 84 which can incorporate heterometals to form MFe 3 S 4 units of probable cubane structure, 85 and establishment of a NiFe 3 S 4,5 cluster in nickel-containing carbon monoxide dehydrogenase. The latter is exemplified by the core reaction sequence [ 8 ] Figure Because summary accounts of synthetic 23 , 89 , 96 — 99 and protein-bound MFe 3 S 4 clusters likely formed by fragment condensation 85 , 99 and a theoretical examination of electronic structure are available, only certain of these clusters useful in the synthesis of higher nuclearity species are further considered.
Isoelectronic vanadium and molybdenum chloride clusters 39a and 39b , respectively, are accessible by the substitution reaction and assembly reactions [ 9 ] in Figure Displacement of chloride with PEt 3 in reaction [10] yields 40a and 40b. Here and elsewhere, mixed oxidation states imply delocalized structures. Synthesis of edge-bridged double cubanes 41 , 42 and P N -type clusters 43 using self-assembly [9], Mo , ligand substitution [10], [11], [13] , fragment condensation [12], and core rearrangement [14], [15] reactions.
Edge-bridged double cubanes are the next structure type of increased nuclearity built only from single cubanes. Thereafter, efficient ligand substitution and self-assembly reactions leading to the isoelectronic chloride single cubanes 39a and 39b , respectively, have been developed. We recapitulate this scheme, which has been described in detail previously. Thereafter, reduction of the phosphine clusters leads to the neutral isostructural EBDC clusters 41a and 41b by the reactions [12].
EBDC clusters present certain characteristic properties. This feature contributes to the stability of the double cubane arrangement. A similar series is likely but has not been established for vanadium clusters. This matter notwithstanding, the procedure in Figure 11 allows straightforward isolation of EBDCs 41 and Clusters 43a and 43b are the second high-nuclearity cluster type accessible by the scheme in Figure The core may be conceptualized as two distorted MFe 3 S 4 cubanes with a common vertex and further supported by two sulfide bridges.
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Comparison of 43a and 43b with the structurally characterized clusters of nitrogenase in Figure 12 , — immediately reveals a structural relationship between the synthetic clusters and the P N cluster. The synthetic and native clusters are both composed of two distorted cubanes sharing a common vertex with a large Fe-S-Fe external angle. Further comparison of the synthetic and native clusters by superposition of crystallographic coordinates reveals a convincingly close topological relationship between the two.
They are not, however, chemical analogues because of the presence of heterometals whereas the P N cluster is all-iron in content. As will be seen Section 6. Schematic structures of the clusters of nitrogenase: During catalysis, the all-ferrous P N cluster is believed to transfer electrons to the catalytic site FeMo-co from the Fe 4 S 4 cluster of the iron protein of the enzyme complex.
Beyond terminal heteroligation and heterometallic core composition, cluster vertices can also be differentiated through core heteroligation. Isolation of mixed-ligand clusters was not attempted. This work was part of any early exploration of cluster reactivity; the mechanism of core atom exchange remains unestablished. Focused interest in core heteroligated clusters is a more recent development motivated in part by the discovery of an interstitial atom X in the[MoFe 7 S 9 X] core of the FeMo-cofactor 44 of nitrogenase.
Unlike heterometallic M-Fe-S cluster synthesis, for which extensive study has yielded several independent and rational preparative strategies, the inverse goal of heteroligated core construction has received only limited systematic attention to date and remains very much a standing challenge. A number of tactical issues are immediately evident. At this juncture, the deliberate installation of any heteroatom, whether as a discrete monoatomic ligand or as a substituted derivative, constitutes a reasonable and essential first step in synthetic discovery.
Cubane clusters with mixed tert -butylimide-sulfide core ligation can be obtained according to the syntheses in Figure The syntheses of the Fe-NR-S clusters are selective, with each specific composition accessible by a separate and distinct reaction route, using reaction sequences that rely on previously developed iron-N-anion cluster chemistry to furnish the imide ligands in the final products.
The mixed core species share basic physical properties and trends with the previously characterized homoleptic cores. The cluster structures combine the specific geometric characteristics associated with imide and sulfide core ligation; e.
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- Developments in the Biomimetic Chemistry of Cubane-Type and Higher Nuclearity Iron-Sulfur Clusters.
- Developments in the Biomimetic Chemistry of Cubane-Type and Higher Nuclearity Iron-Sulfur Clusters.
Under ambient conditions, individual clusters of a given mixed core composition do not disproportionate to other core heteroligand compositions, and mixtures of clusters of different core compositions do not give rise to new core compositions. Within the heteroleptic series, monoimide trisulfide cluster 47 is particularly notable in possessing a core Fe 4 NS 3 framework that superposes closely onto the Fe 4 S 3 X portion of FeMo-co Figure Using an alternative strategy adapted from recent Fe 4 S 4 chemistry Section 3. The bridging core imide is reactive and can be selectively replaced by less basic arylimides via transamination with arylamine to form This behavior follows known reactivity in certain iron-imide clusters, , but equivalent chemistry has not been demonstrated in iron-sulfur systems.
Reactions of 47 illustrating core retention under terminal ligand substitution, oxidation and reduction, and replacement of the core imide by transamination with an arylamine to afford All routes can be classified descriptively as fragment condensations according to the introduced reactants, and hypothetical balanced equations can be formulated based on experimental stoichiometries. Aspects of the precursor structures can be discerned in the final products, and the reactions themselves are moderately to highly selective for their respective core heteroligand compositions.
These observations suggest that the empirical descriptions of fragment condensation in these systems might also apply to underlying mechanisms. The cluster assembly pathways for these systems remain unknown at present. More recently, the oxide-containing octanuclear cluster 58 has been synthesized by treatment of a diferrous thiolate alkoxide precursor 57 obtained from the curious mononuclear complex 56 with a mixture of water and elemental sulfur Figure A second, structurally-related octanuclear product 59 is also formed.
The two clusters were isolated as a mixture by HPLC, with crystallization yielding oxide-containing 58 with variable levels of 59 as a co-crystallized contaminant. The iron enviroments are either explicitly tetrahedral five sites or implicitly tetrahedral two sites and trigonal bipyramidal one site if more distant iron-arene interactions are included in the metal coordination spheres. The topology resembles the FeMo-co connectivity and is discussed with other examples in Section 6. The similarities between the two reaction products suggest that both 58 and 59 arise from the same or closely related cluster assembly pathways, with hydrolysis from introduced water leading to the oxide-containing core.
Selenide is an effective structural and electronic analogue of sulfide in iron-sulfur chemistry, and recent progress has demonstrated its selective incorporation into M-Fe-S clusters. One procedure utilizes the trisulfido complexes 60 in the self-assembly redox system [20] in Figure In comparing the various Fe 4 S 3 Q and MFe 3 S 3 Q cores encountered thus far, perhaps the most impressive aspect is the range of Fe-Q distances permitted by the cubane-type geometry, albeit distorted by Q atom radius differences.
Core conversion reactions [14] and [15] Figure 11 can be minimally described by reaction [ 21 ] in which hydrosulfide is an external nucleophile. Because multiple core bonds are made and broken, the reaction pathway is not evident. However, an issue necessary to any ultimate mechanism that can be addressed is the locus of the attacking nucleophile in the product cluster. It utilizes the pronounced chemical similarity between sulfur and selenium in the same oxidation state and their ready distinction by crystallography.
The structural fate of sulfide or selenide, both as an external and internal bridging nucleophile, has been further examined in the formation of four cluster types in Figure This species presents three terminal sulfide nucleophiles as a template for self-assembly, here leading to single cubanes and hexanuclear cluster cores W 2 Fe 6 S 9 of a new structural type. The left-hand column demonstrates analogous reactions of molybdenum and tungsten clusters leading to the P N -types 64a and 64b. With 66 and hydroselenide, the P N -type core 68 with three selenide bridges between the cubanes is produced.
Simplified scheme showing the positions of incorporation of bridging selenide atoms in four different types of cluster cores as determined by X-ray structure analysis adapted from ref. Terminal ligands omitted for clarity are the following: The research summarized in Figure 18 has two goals: The formation of single cubanes together with the assembly of double-cuboidal clusters is ample evidence of the efficacy of the WS 3 group of 63 in template-assisted synthesis. Note that in all products selenium is bound only to iron, indicating that the WS 3 group remains intact.
Nonetheless, if the premise holds that selenide is a true surrogate of sulfide in molecules with equal numbers but differing populations of chalcogenides, the behavior of sulfide in sulfur-only reaction systems is revealed. One caveat is that the ca. However, the well-documented structural analogy between Fe-S and Fe-Se clusters, including single cubanes, 11 , 48 , , renders this situation unlikely. No such structural effect has yet been observed.
The many similarities in the molecular chemistry of molybdenum and tungsten make it likely that the results obtained here would apply to Mo-Fe-S clusters as well. Although these two cases involve very different reaction types and are therefore not strictly comparable, the strength of heavy metal-ligand i. Selenide, whether introduced as an exogenous reactant or occurring as an internal ligand prior to core rearrangement, never disrupts a pre-existing W-S interaction.
A number of examples appear elsewhere, including the alkoxide- and thiolate-bridged Fe 8 S 7 clusters Sections 5. Bridges currently include monoanionic S-, O-, and N-donors thiolate, alkoxide, and amide, respectively and dianionic chalcogenides oxide and selenide. In the present context, thiolate, in contradistinction to sulfide, is a heteroligand. Recent cluster types post containing these bridging ligands are depicted, together with synthetic summaries, in Figure Several types of recent heteroligand-bridged clusters are recognized: Schematic structures of synthetic Fe 8 S 7 clusters: Also shown is the Fe 8 portion of 78 as an idealized bicapped trigonal prism with the mean Fe-S bond distance and mean length of Fe-Fe edges in trigonal faces; lengths of other Fe-Fe edges are indicated adapted from ref.
The foregoing clusters may be distinguished from others such as the diclusters 75 , , , , and the tricluster For this class, bridging results in more open or flexible structures that are better described as bridged assemblies , a concept previously introduced. Cores 32 and 33 Figure 10 are further examples of homo- and heteroligated assemblies, respectively.
While there is no absolute demarcation between clusters and bridged assemblies, especially in the case of structurally complex, high-nuclearity structures, the former are typically distinguished by intimately bridged, compact frameworks whereas the latter possess obvious i. These self-assembly systems are conventionally performed in methanol or nonprotic polar solvents, mainly acetonitrile, dichloromethane, DMF, or Me 2 SO. Not surprisingly, the success of early assembly reactions — such as [ 22 ], , [ 23 ], and [ 24 ] , has stimulated development of other successful cluster syntheses with ionic reactants in polar solvents.
Note that in these systems, thiolate acts as a reductant of Fe III , Mo VI , and elemental sulfur, a frequent feature of assembly reactions containing these reactants. Such systems in general are useful in producing charged clusters of varying nuclearity. Such systems provide three conditions favorable to the formation of large metastable clusters: Schematic structures of product clusters 77 - 79 are provided in Figure 20 and bear comparison with the nitrogenase clusters 44 - 46 Figure Sulfide appears to be removed as S 0 from the initial cluster core, a rare reaction for any iron-sulfur cluster that is likely facilitated in this instance by the all-ferric oxidation state of the precursor.
The net reaction couples two precursor clusters by means of sulfur removal and is a creative application of the fragment condensation concept. The amide provides bridging and terminal ligation and the thiourea or phosphine sulfide is terminally coordinated. Note that thiolate does not appear in either product. Other than noting that the P OX cluster has access to additional coordinating protein ligands, it is unclear why this cluster and 77a and 77b have very different core structures. The most remarkable aspect of these species is the presence of an interstitial sulfur atom contained within a severely distorted Fe 6 trigonal prism Figure This feature associates 78 and 79 with alkoxide-bridged cluster 59 Figure In 78 , the two Fe-Fe edges of the prism bridged by SDmp are much longer 3.
As recognized by Ohki et al. A cluster of this composition with two thiolate bridges would closely simulate the native P N cluster 46 with two cysteinate bridges and corresponding terminal ligation. The shape of the Fe 6 trigonal prism of the cofactor is more regular, all Fe-Fe edge lengths being in the 2. The cofactor has been shown to incorporate an interstitial carbide Section 5. However, the host polyhedron is octahedral rather than trigonal prismatic, and the iron oxidation state is much reduced compared to the cofactor for which various assessments have led to a mean oxidation state in the range Fe 7 2.
In nonpolar solvents like toluene, the formation of charged products is suppressed. With suitable empirically-determined reaction stoichiometries, uncharged clusters can form under these nonpolar conditions, although predictive powers are so limited that the nuclearity of the products and other structural features must be left to experiment. In the synthesis of 77 — 79 , stepwise cluster buildup must occur, but the steps are unknown.
The authors of this work do not propose balanced equations for cluster formation, perhaps because of competing reactions and lower yields in some cases. While much remains to be learned, the synthesis of Fe 8 S 7 clusters is a noteworthy achievement in the biomimetic chemistry of iron-sulfur clusters. In bioinorganic enzymology, all aspects of catalytic sites--from biosynthesis to reaction mechanisms--are subjects of contemporary inquiry.
This account is concerned with synthesis, and by possible implication, the biosynthesis of certain types of metalloclusters. The foregoing sections describe the current state of biomimetic metal chalcogenide and imide cluster chemistry implicating species of nuclearities four and eight. Clusters with cubane-type [Fe 4 S 4 ] z cores are emphasized because these structures are ubiquitous in biology and enjoy an import comparable to other prosthetic groups such as hemes and flavins.
Throughout, emphasis has been placed on original methods of synthesis because this is the most challenging part of the synthetic analogue approach to biological metal sites. The synthesis of biologically relevant metalloclusters addresses two primary goals. The first is to determine in as much detail as possible how a given cluster is formed. In a biological system, this requires the elucidation of the overall reaction pathway , which describes the order of events and the proteins and other reactants necessary at each stage of cluster assembly.
Thereafter, the chemical mechanism which includes atom-by-atom, even electron-by-electron, events is sought. While the sequence of events in the biosynthesis of any metallocenter is presumably controlled by proteins, it seems probable that the step-by-step formation of the final cluster implicates reactivity properties intrinsic to the reactants that form the core structure.
In this context, we repeat an earlier statement: A second goal is the exposition from a credible representation of a biological cluster of intrinsic structural, electronic, and reactivity properties. Differences may then be a consequence of protein environment. While the mechanism of any biological reaction must be extracted from the protein itself, reactivity properties of a synthetic cluster may, at the least, show what is possible.
Lastly, any ultimate description of cluster biosynthesis must rely on demonstrated inorganic chemical reactivity. These include cluster assembly with an Fe II salt and a persulfide [ 25 ] , fragment condensation by reductive core dimerization [ 26 ] , and ligand substitution to bind the core to the protein [ 27 ].
The intention of much of the work described here is to extend this understanding of fundamental cluster reactivity. Without such research, there is no way to know what is possible. Presently, the sequential pathways and component proteins involved in the biosynthesis of simple iron-sulfur clusters and FeMo-co are emerging, but the mechanisms of biological cluster assembly remain largely unknown at the molecular level. He received his chemical education at Caltech B. Gray and Harvard University Ph.
Holm , and is currently a faculty member at the University of Waterloo. His research interests emphasize aspects of synthetic inorganic chemistry, particularly the preparation and study of clusters containing weak-field iron centers and nitrogen anions as biomimetic analogues for the cluster chemistry of biological nitrogen fixation. Wayne Lo was born in Taipei, Taiwan. He worked as postdoctoral associate with Professor R. Holm at Harvard University — His research interests are in inorganic and bioinorganic chemistry, with emphasis on metalloenzymes with iron-sulfur and manganese clusters and the design of biologically related metallocompounds.
Holm was born in Boston, Massachusetts. He spent his early years on Nantucket Island and in Falmouth, Massachusetts where he received his secondary school education. He is a graduate of the University of Massachusetts B. His graduate advisor was Professor F. As of , he has been Higgins Research Professor of Chemistry. His research interests are centered in inorganic and bioinorganic chemistry, with particular reference to the synthesis and properties of molecules whose structures and reactivity are relevant to biological processes.
1. Introduction and Scope
With Professor Edward I. Solomon, he has been co-editor of three thematic issues in Chemical Reviews: The authors declare no competing financial interest. National Center for Biotechnology Information , U. Author manuscript; available in PMC Apr 9. Author information Copyright and License information Disclaimer. The publisher's final edited version of this article is available at Chem Rev. See other articles in PMC that cite the published article.
Introduction and Scope A prior thematic issue of Chemical Reviews in 1 provides broad coverage of the field of biomimetic inorganic chemistry. Open in a separate window. West Sussex, England, Primary dehydrogenases, some of which are complex Fe-S enzymes, provide the reducing equivalents from the respiratory substrates such as succinate, NADH, and sulfide to the central caldariellaquinone pool in the tetraetherlipid membrane [ 35 , 68 , 71 , 74 , 75 ]. The archaeal respiratory chains may be in fact archaic, but not so primitive as they had seemed two decades ago.
For instance, the S. Additionally, while the terminal oxidase supercomplexes of S. Thus, the Sulfolobus aerobic respiratory chain in a mechanistic context is still in its infancy compared with the mitochondrial and bacterial tractable model systems, and needs to be explored in future studies. In the thermoacidophilic archaea, the transmembrane pH-driven secondary transporters for peptides, sugars, and inorganic compounds are preferred over primary ABC transporter systems [ 19 — 21 ], which is not surprising given a permanent huge pH across the membrane.
Available genomic sequences of the Sulfolobus species [ 74 , 75 , 79 , 93 ] suggest the presence of metal transporter homologs [ 20 , 22 , 94 , 95 ], some of which may be involved in trafficking iron ions for the biogenesis of Fe-S proteins.
2. General Tactics in Cluster Synthesis
Very little is known to date about in vivo iron-trafficking and homeostasis systems in these archaea e. In contemporary bacteria and eukarya, the de novo Fe-S cluster biogenesis and maturation in vivo have been shown to require specific enzymes in the carefully regulated Fe-S cluster biosynthesis systems [ 5 , 7 — 9 , 96 — ], while spontaneous assembly of the Fe-S clusters does occur in vitro.
At least three types of the Fe-S cluster biosynthesis systems ISC i ron s ulfur c luster , SUF mobilization of su l f ur , and NIF ni trogen f ixation are known, with significant variations in terms of the phylogenetic distribution [ 7 , 99 — ]. In the eukaryal domain [ 7 , 8 ], ISC homologs are found to be localized largely in mitochondria, while SUF homologs are found in some chloroplasts.
It is therefore possible to postulate that the mitochondrial ISC system originated from the endosymbiotic bacterial ancestor and the plastid SUF system from the cyanobacterial ancestor. In these tractable model organisms, the regulation of biological Fe-S cluster assembly is further complicated by the involvement of other accessory proteins required for the in vivo function [ 7 , 8 , 99 , , , ], and is not fully understood.
While pyridoxal phosphate-containing cysteine desulfurases utilize L-cysteine for mobilization of S for Fe-S core formation, there is as yet no consensus concerning immediate iron donor for Fe-S cluster assembly.
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Disruption of the E. The components of the suf operon has been shown to be preferred for Fe-S cluster biosnthesis under oxidative stress conditions [ , ] and during iron starvation [ ] although the ISC and SUF systems are principally interexchangeable, especially in an anaerobic environment [ ]. In some hyperthermophilic archaea and bacteria, the SUF system has been proposed to be the sole pathway for cluster assembly [ 98 , ].
This implies that some components of the hyperthermophile SUF-related system might represent a primordial pathway for the Fe-S cluster biogenesis. Although aerobic and anaerobic archaea produce numerous Fe-S proteins, the major components of the bacterial and eukaryal Fe-S cluster biosynthesis systems are not universally conserved in archaea. No sufA homolog could be identified in this archaeal genomic sequence [ 74 , ]. This is in line with a detection of archaeal SufBCD complex by the native proteome approach from native biomass using P.
While SufA is absent in most archaea [ ] Figure 2 , bottom , the homologs of the bacterial apbC [ , ] and eukaryotic NBP35 [ , ] genes, coding for Fe-S cluster carrier proteins, are conserved in some archaea [ ] ST in the S. Likewise, the eukaryal ApbC homologs Cfd1 and Nbp35 form the extramitochondrial homotetrameric complex, and bind labile [4Fe-4S] clusters after in vitro reconstitution , which can be transferred to target Fe-S apoproteins but only when other CIA c ytosolic i ron-sulfur protein a ssembly proteins Nar1 and Cia1 co-exist [ ].
For example, an archaeal SufS homolog was recently identified from Haloferax volcanii [ ] and a possible CsdA but not SufS homolog is found in the genomic sequence of Aeropyrum pernix K1 APE [ ] , but they are poorly conserved in S. Thus, an alternative possibility is still open for novel cysteine desulfurases in these archaeal SUF systems. There are very few genetic and biochemical studies e. As described briefly in the preceding section, the de novo Fe-S cluster biosynthesis, which is catalyzed and regulated by a number of specific enzymes, can be divided into two major steps Figure 2.
The first step is a transient de novo Fe-S cluster assembly on a scaffold protein requiring sulfur and iron donors. In the second step, the transient Fe-S cluster is dislocated from the scaffold protein, followed by transfer and insertion into recipient apoproteins, either during or shortly after the apoprotein generation and before the folding into its native-like conformation.
Rieske-type [2Fe-2S] clusters are ubiquitous in a variety of organisms, playing crucial electron transfer functions in respiratory chains, photosynthetic chains, and multicomponent oxygenase systems for biodegradation of aromatic and alkene compounds [ 85 , , ]. The structure of a bovine mitochondrial Rieske protein domain fragment suggests that its cluster-binding loops have a similar geometry to those found in the rubredoxin and zinc ribbon scaffolds [ ]. We have addressed the influence of substitution of each of the two outermost histidine ligands His44 and His64 by cysteine on the properties of the Rieske-type [2Fe-2S] cluster in S.
Replacement of the two histidine ligands to the [2Fe-2S] cluster of S. These experiments demonstrate that the in vivo assembly of a [2Fe-2S] cluster in the Rieske protein scaffold is determined primarily by the nature and spacing of the ligands at the cluster binding loops which are often located near the protein surface in modular Fe-S proteins [ , ] Figure 3.
Iron-Sulfur World in Aerobic and Hyperthermoacidophilic Archaea Sulfolobus
The two innermost cysteinyl ligand residues Cys42 and Cys61 of S. This is in accord with the previous report by Meyer et al. Here the minimal requirement for the number of terminal cysteinyl ligands to a cubane [4Fe-4S] cluster is usually three in most simple and complex Fe-S proteins, and the fourth ligand at a spatially particular position can be an external ligand [ 2 ] e. Contemporary aerobic and thermoacidophilic archaea inherited the resultant intracellular Fe-S world from their anaerobic ancestors, and this world keeps running in an extraordinary environment by powering the enzyme-assisted Fe-S cluster biogenesis machinery.
The majority of thermophilic archaea are anaerobic organisms because molecular oxygen is often scarce in their habitats. Early biochemical evidence has established that one of the characteristic features in the central metabolic pathways of both anaerobic and aerobic archaea is the involvement of ferredoxins in electron transport. In the aerobic and thermoacidophilic archaea, zinc-containing ferredoxin [ 17 ] is abundant in the cytoplasm and functions as a key electron carrier; in addition, many other Fe-S enzymes are operative in the central metabolic and bioenergetic pathways [ 17 , 35 , 68 ].
These Fe-S proteins must be protected by keeping intracellular pH at an acceptable value typically 5. Thus, in addition to expected structural adaptations of a local Fe-S cluster binding site by natural selection, the Fe-S enzymes of aerobic and thermoacidophilic archaea obligately require the stringent intracellular pH homeostasis mechanism, as well as the reactive oxygen species-scavenging system.
Some thermoacidophilic archaea such as Thermoplasma do this by reducing the proton influx by the generation of an inside positive membrane potential , which is generated by a difference in electrical potential formed between a greater influx of cations such as potassium ions and the outward flux of protons [ 19 , 21 , 59 ]. In Sulfolobus , the inside negative is rather low and the PMF is largely composed of a pH of greater than 2 units [ 21 , 58 , 60 , 68 ], where the cognate aerobic respiratory chain probably fulfills the role as an effective proton pump in vivo and preserves the cognate Fe-S world descendant from their anaerobic ancestors.
De novo formation of intracellular Fe-S clusters does not occur spontaneously but requires specific biosynthetic pathways: More specifically, only the SufB, SufC, and SufD homologs are conserved in some archaea including Sulfolobus , which most likely function as a putative Fe-S scaffold complex [ , ]. In many recipient Fe-S protein modules, the Fe-S cluster is assembled to loop regions and is often located near the protein surface. The in vivo assembly of a biological Fe-S cluster in a recipient protein scaffold is determined primarily by the nature and spacing of the ligands in the cluster binding loops.
I hope that this short review will stimulate further research work, through which the answers to many open questions will be integrated into a comprehensive view on the biogenesis and maintenance of the archaeal Fe-S world. The author would like to thank numerous colleagues and collaborators whose names appear in the references, and Professor Tairo Oshima and Professor Takeshi Nishino, whose support over many years is gratefully acknowledged. Indexed in Science Citation Index Expanded. Subscribe to Table of Contents Alerts.
Table of Contents Alerts. Abstract The general importance of the Fe-S cluster prosthetic groups in biology is primarily attributable to specific features of iron and sulfur chemistry, and the assembly and interplay of the Fe-S cluster core with the surrounding protein is the key to in-depth understanding of the underlying mechanisms.
Zinc-Containing Ferredoxins Are Abundant in the Aerobic and Thermoacidophilic Archaeal Cells The physiological significance of bacterial-type ferredoxins in the aerobic and thermoacidophilic archaea, such as Sulfolobus and Thermoplasma , was first recognized by Kerscher et al. Comparative structures by superposition of archaeal zinc-containing ferredoxins from S. In panels a and c , key residues are labeled; pink asterisk indicates the special iron of the cluster II, which is missing in the 6Fe form 1xer.
Tanaka, unpublished results] b. Schematic illustration of the cysteine desulfurase CDS -mediated, transient Fe-S cluster assembly on Fe-S cluster scaffold proteins and subsequent cluster transfer to various target apoproteins [ 7 , 99 , ] top , and the organization of the suf gene clusters annotated in the E. Multiple sequence alignment of the metal-binding sites of selected Rieske-type proteins and rubredoxins Rd. The cluster-binding motif of S.
The metal-binding motifs are underlined left , and the structure of the cluster ligand residues of a bovine mitochondrial Rieske protein domain fragment PDB code, 1rie. View at Google Scholar H. View at Google Scholar K. View at Google Scholar F.