bluuebunny/crossref_metadata_2025_split huggingface dataset:
The 2[4Fe–4S] Ferredoxins
Authors: Sieker Larry C , Adman Elinor T 
Published: April 2006

AbstractThe 2[4Fe4S] ferredoxins, that are members of the ‘clostridial’ and ‘chromatium’ classes of bacterial ferredoxins, have two cuboidal 4Fe4S clusters each in which each iron is coordinated by three inorganic sulfurs and one cysteinyl sulfur. The protein chains (54–80 amino acids) have internal homology so that the environments of each cluster are similar, and the 12.5 Å center‐to‐center separation of the clusters permits electronic interaction. These proteins participate in electron transfer systems, and, characteristically, have very low redox potentials. NH‐S hydrogen bonds, peptide dipole orientations, and solvent accessibility are among factors that have an effect on the oxidation–reduction potential. In that regard, a ‘spine’ of water molecules seems to be a conserved structural component linking the β‐sheet in each half of the molecule for all the ferredoxins in this class. Site‐directed mutagenesis studies have been carried out to analyze redox potentials, stability, intermolecular interactions, and intramolecular electron transfer.
Methane Monooxygenase Hydroxylase
Authors: Whittington Douglas A , Lippard Stephen J 
Published: April 2006

AbstractSoluble methane monooxygenase (sMMO) catalyzes the conversion of methane and dioxygen to methanol and water. It is a cytoplasmic system of three proteins produced in methanotrophic bacteria grown under conditions of low copper stress. The best characterized sMMO stems fromMethylococcus capsulatus(Bath). Under physiological conditions inM. capsulatus(Bath), three protein components are required for sMMO activity. These included a 251‐kDa hydroxylase (MMOH), which contains the carboxylate‐bridged, dinuclear iron active site; a 16‐kDa regulatory protein known as protein B (MMOB); and a 38.6‐kDa reductase (MMOR) that contains FAD and a Fe2S2center. MMOH has been characterized by several spectroscopic techniques (UV/vis, X‐ray absorption, Mössbauer, EPR, ENDOR, CD, MCD), which established the nature of the dinuclear iron active site.The crystal structure of the MMOH component of sMMO fromM. capsulatus(Bath) has been solved in two crystal forms, one of which was refined to a resolution of 1.7 Å. The enzyme is composed of two copies each of three subunits (α2ß2γ2), and all three subunits are almost completely α‐helical. The active site of each α‐subunit contains one dinuclear iron center, housed in a four‐helix bundle. The two iron atoms are octahedrally coordinated by 2 histidine and 4 glutamic acid residues, as well as by a bridging hydroxide ion, a terminal water molecule, and at 4°C, a bridging acetate ion, which is replaced at −160°C with a bridging water molecule. Comparison of the results of the two crystal forms shows one structural difference, namely, the altered side chain conformation of Leu110 at the active site cavity. It is suggested that this residue serves as one component of a hydrophobic gate controlling the access of substrates to and products from the active site. MMOB and MMOR bind to the α‐ and ß‐subunits of MMOH, respectively. The structure of MMOB has been known from NMR. X‐ray structures of reduced MMOH and of DMSO‐soaked MMOH have been determined. During the turnover, Hperoxoand Q intermediate states could be trapped and structures proposed from density functional theory studies.
Iron‐Only Hydrogenases
Authors: Lemon Brian J , Peters John W 
Published: April 2006

AbstractThe Fe‐only hydrogenases, also termed FeFe hydrogenases, catalyze reversible hydrogen oxidation and occur in various microorganisms and a few lower eukaryotes. These enzymes are complex FeS enzymes with unique organometallic biological activity. The Fe‐containing cluster at the active site, termed the H cluster, consists of a complex bridged metal cluster assembly with a [4Fe‐4S] subcluster linked to a 2Fe subcluster containing a unique non‐protein dithiolate linkage and both carbon monoxide and cyanide ligands. Because of the novelty of the active site H cluster, the enzyme has been a very interesting topic for experimental analysis by using a variety of physical methods. This chapter describes methods to probe the activity and electronic structure properties of Fe‐only hydrogenases and the state of the understanding of the mechanistic features of the enzymes based on data compiled to date.
Lactoferrin
Authors: Smith Clyde A 
Published: April 2006

AbstractLactoferrin, a member of the transferrin family of proteins, plays an important role as a regulator of the levels of free iron in the body fluids of mammals. The ability to bind Fe3+with high affinity (theKDis approximately 10–20M) and also to retain it to low pH, gives the protein both bacteriostatic and antioxidant properties. A detailed knowledge of the three‐dimensional structure of lactoferrin makes it possible to understand these properties. The lactoferrin molecule is folded into two homologous lobes (N‐ and C‐lobes), each lobe being further divided into two domains. Each lactoferrin molecule is able to bind two metal ions, one in each lobe; the metal binding sites are in the deep cleft formed between the two domains, and metal binding is always associated with the concomitant binding of a carbonate anion. Despite the very high affinity for iron, lactoferrin is nevertheless able to bind a surprisingly wide variety of other metal ions including aluminium and gallium, transition metals such as vanadium, manganese, copper, ruthenium and cadmium, along with the rare earth metals and some actinides. Structural details are known for some of these metal complexes, including Cu2+, Ru3+, Ce4+, and Sm3+, and also for complexes containing an oxalate anion rather than the typical carbonate. It is known that iron binding and release are associated with large conformational changes in which the protein adopts either an open or closed state. Comparisons of structural and functional data on lactoferrins and transferrins now suggest that the key factor comes from cooperative interactions between the two lobes of the molecule, mediated by two α‐helices.
The Ferric Hydroxamate Uptake ReceptorFhuAand RelatedTonB‐Dependent Transporters in the Outer Membrane of Gram‐Negative Bacteria
Authors: Ferguson Andrew D , Coulton James W , Diederichs Kay , Welte Wolfram 
Published: April 2006

AbstractFhuA, receptor for ferrichrome‐iron inEscherichia coli, is a member of a family of integral outer membrane proteins, which together with the energy transducing TonB–ExbB–ExbD complex of the cytoplasmic membrane, mediate active transport of siderophores, Vitamin B12, and heme across the outer membrane of gram‐negative bacteria.In addition to transporting ferrichrome, FhuA acts as the primary receptor for several bacteriophages, the antibiotics albomycin and rifamycin CGP 4832, the cyclic peptide antibiotic microcin J25, and the bacterial toxin, colicin M.FhuA is a β‐barrel composed of 22 antiparallel β‐strands. Located within the β‐barrel is a structurally distinct domain, the ’cork’, consisting mainly of a four‐stranded β‐sheet and four short α‐helices. The focus of this review is an analysis of the relationship between the three‐dimensional structure of FhuA and its biological function as an energy‐dependent outer membrane transporter.
Nickel–Iron Hydrogenases
Authors: Frey Michel , Fontecilla‐Camps Juan C , Volbeda Anne 
Published: April 2006

AbstractNi–Fe hydrogenases catalyze the cleavage or the production of the most simple of chemical compounds, molecular hydrogen. This review provides an overview of the literature on these enzymes that has been published before the year 2000. On the basis of atomic models plausible pathways of substrates and products are described, including a hydrophobic tunnel network for H2diffusion, a suitable arrangement of three iron–sulfur clusters for electron transfer, a network of buried water molecules, and a magnesium site that could be involved in proton transfer. A combination of protein crystallography, electron paramagnetic resonance, and Fourier transform infrared spectroscopic studies has allowed the elucidation of the unique architecture of the active site. This consists of a thiolate‐coordinated Ni–Fe unit involving one carbon monoxide and two cyanide ligands to the iron, leaving two metal coordination sites available for substrate binding. Understanding the catalytic mechanism of these fascinating enzymes might be helpful for the development of cheap catalysts for fuel cells working on H2or of cheaper production methods for this clean fuel.
Peptide Deformylase
Authors: Becker Andreas , Kabsch Wolfgang 
Published: April 2006

Abstract

Peptide deformylase (EC 3.5.1.31) is a mononuclear iron enzyme that cleaves the formyl group of the
N
‐terminal formyl‐methionine residue of nascent polypeptide chains in eubacteria. It is strictly stereospecific for a
L
‐amino acid as the first residue of formyl‐peptide substrates and strongly prefers substrates with at least two or more residues. The native enzyme from

Escherichia coli

is a monomeric protein of 168 amino acid residues that contains one tightly bound Fe
2+
ion. The metal ion is tetrahedrally coordinated by a water molecule and the side chains of residues Cys90, His132, and His136. Similar to thermolysin, the two histidines are part of the HEXXH motif and the glutamate residue is required for enzymatic activity. The native iron form of peptide deformylase is extremely sensitive to oxidative destruction. On substitution of the iron ion by Ni
2+
or Co
2+
the enzyme is insensitive to oxidation and maintains its activity, whereas the Zn
2+
form is nearly inactive.
Diphtheria Toxin Repressor: Metal Ion Mediated Control of Transcription
Authors: Ringe Dagmar , White Andre , Chen Shuyan , Murphy John R 
Published: April 2006

AbstractThe diphtheria toxin repressor is a metal ion–activated DNA‐binding protein that prevents transcription of the diphtheria toxin gene. In its active form the repressor interacts with a semi‐palindromic operator sequence as two noninteracting dimers that recognize overlapping sequences. Recognition of the sequence occurs through two base‐specific interactions. The dimer binds two metal ions per monomer in its active form, only one of which is essential for DNA binding. The mechanism by which activation occurs includes the unraveling of the first turn of the N‐terminal helix in an indirect interaction with the critical metal ion that allows the repressor to interact optimally with the operator sequence of the toxin gene.
Arginase
Authors: Bewley Maria C , Flanagan John M 
Published: April 2006

AbstractArginase is a manganese hydrolase related to agmatinases, formiminoglutamases, and proclavaminate amidino hydrolase. It hydrolyzes L‐arginine to L‐ornithine and urea and occurs in bacteria, yeast, plants, invertebrates, and vertebrates. In mammalian species cytosolic type I and mitochondrial type II arginase are found. Type I arginases, located in the liver, catalyze the final step in the urea cycle. Type II arginases are extrahepatic and catalyze the same reaction as type I arginases, but due to their cellular location, give rise to different biological functions that center on regulating the levels of L‐arginine or L‐ornithine. For example, they are thought to regulate the concentrations of L‐arginine, a biosynthetic precursor of nitric oxide (NO), and thus, participate in the NO signaling pathway. By controlling the concentration of L‐ornithine, they affect the biosynthesis pathway of glutamate, proline, and polyamines. Arginase monomers have molecular weights of about 30 to 40 kDa and generally function as homo‐oligomers. All spectroscopic measurements have been made using the rat liver arginase and the Mn(II) EPR spectra are typical of μ‐ligand bridge spin‐coupled Mn2(II,II) centers.Crystal structures of rat andBacillus caldoveloxarginases have been determined. Rat liver arginase is a homotrimer. Each monomer of 323 amino acids has a globular shape and comprises an eight‐stranded parallel ß‐sheet packed on either side by helices to form a single α/ß domain. Each monomer contains its own active site. Two catalytic manganese ions, MnAand MnBare located at the bottom of the active site. MnAis coordinated by a histidine, three aspartates, and two water molecules. MnBis also coordinated by a histidine and three aspartates but by one water molecule only. One of the aspartates is bidentately coordinated (MnB), two others bridge both Mn ions, one with one side chain oxygen to both Mn ions, the other one with each side chain oxygen individually to each Mn ion. Both Mn ions display an octahedral coordination. TheB. caldoveloxarginase is a homohexamer with 32 point group symmetry. Each monomer contains 299 amino acid residues. Overall fold and active site geometry is very similar to that of the rat enzyme. Crystal structures of arginases in complex with L‐arginine, L‐lysine, L‐ornithine, and 2(S)‐amino‐6‐borohexanoic acid (ABH) have been determined and have helped, together with kinetic studies, to formulate a structure‐based catalytic mechanism for arginase in parallel to an EPR‐based mechanism.
Concanavalin
A
Authors: Kalb (Gilboa) A Joseph , Helliwell John R 
Published: April 2006

Abstract

Concanavalin A is a metalloprotein containing manganese and calcium in a bimetallic metal‐binding site. As isolated from the Jack bean (

Canavalia ensiformis

), the protein binds saccharides such as α‐methyl mannoside and α‐methyl glucoside. Acid treatment produces a demetallized form that does not bind saccharides and that which can be remetallized to produce various metal‐substituted forms, such as (Ni, Ca), (Co, Ca), (Cd, Ca), (Zn, Ca), and (Cd, Cd). Structural studies of the crystal structures of the native, demetallized, and remetallized proteins, as well as its complexes with saccharides, have helped clarify the nature of the interaction between the metal‐binding site and the saccharide‐binding site. The protein has been well‐characterized structurally, namely, at an X‐ray crystallographic resolution of 0.94 Å (Mn, Ca form), by neutron protein crystallography to define the hydration details (at 2.4 Å resolution), by molecular dynamics to better define the protein saccharide recognition, by EPR using the manganese d5 high spin state, and by EXAFS (Zn, Ca form). These structural characterizations include studies at 12 K, 100 K, and room temperature.
Aminopeptidase
P
Authors: Guss J Mitchell , Freeman Hans C 
Published: April 2006

Abstract

Aminopeptidase P is a metalloprotease, which specifically cleaves the N‐terminal residue of a peptide if the second residue is proline. The enzyme is a member of the pita‐bread fold family of metalloenzymes that includes methionine aminopeptidase and prolidase.

Escherichia coli

aminopeptidase P is a tetramer in crystals and in solution. Each subunit has a dinuclear manganese (Mn) centre at its active site. A hydroxide ion that bridges the Mn atoms has been identified as the nucleophile in the enzymatic reaction.
Glutamate Mutase
Authors: Kratky Christoph , Gruber Karl 
Published: April 2006

AbstractThe 5′‐adenosylcobalamin–dependent glutamate mutase catalyzes the reversible and stereospecific equilibration of (S)‐glutamate with (2S,3S)‐3‐methylaspartate through a radical mechanism, whose first step consists of homolysis of the cofactor's cobalt–carbon bond. The enzyme occurs in clostridia, where it catalyzes the first step of the fermentation of glutamate. The protein exists as a heterotetramer of composition ɛ2σ2(B12)2, with each of the two B12cofactor molecules located between an ɛ and a σ peptide. There are two substrate‐binding sites per heterotetramer at a distance of about 6 Å from the B12cofactor. The σ peptide folds as an α/β domain and is very similar to the B12‐binding domains of other B12‐dependent enzymes. The ɛ subunit consists of a (β/α)8‐barrel (TIM‐barrel) domain, whose one end packs against the ‘upper’ face of the B12cofactor, thus forming the active site cavity.
Cobalamin‐Dependent Methionine Synthase
Authors: Gruber Karl , Kratky Christoph 
Published: April 2006

AbstractThe methylcobalamin‐dependent methionine synthase catalyzes the transfer of a methyl group from 5‐methyltetrahydrofolate to homocysteine. This constitutes the terminal step in thede novosynthesis of methionine in eubacteria. In mammals, the enzyme is part of a salvage pathway involved in the conservation of limiting amounts of this essential amino acid. TheEscherichia colienzyme is a modular protein consisting of four distinct regions each with a specific function in the overall catalytic cycle. Crystal structures of two of these modules (the B12‐binding fragment and the C‐terminal activation domain) have been determined.
CO
Dehydrogenase
Authors: Dobbek Holger , Gremer Lothar , Meyer Ortwin , Huber Robert 
Published: April 2006

Abstract
Two principal types of CO dehydrogenases have been discovered, which are distinguished by their metal contents, amino acid sequences, molecular masses, and their sensitivity toward dioxygen.

The CODH from the aerobic eubacterium

Oligotropha carboxidovorans

catalyzes the oxidation of CO with H
2
O, yielding CO
2
, two protons, and two electrons. The enzyme is composed of an 88.7‐kDa molybdoprotein (L), a 30.2‐kDa flavoprotein (M), and a 17.8‐kDa iron–sulfur protein (S) and is organized as a dimer of LMS heterotrimers. The active site of CODH consists of a binuclear heterometal [CuSMo(=O)OH] cluster that is prone to cyanolysis. The cluster is coordinated through interactions of the molybdenum with the dithiolate pyran ring of molybdopterin cytosine dinucleotide and of the copper with Sγ of Cys388; the two metals are bridged by a sulfido‐ligand. A model for the catalytic cycle involves a thiocarbonate‐like intermediate state and includes the transfer of two electrons from Mo through two types of [2Fe–2S]‐clusters to the flavin–adenine dinucleotide cofactor.
Amicyanin and Complexes of Amicyanin with Methylamine Dehydrogenase and Cytochromec551i
Authors: Mathews F Scott 
Published: April 2006

AbstractAmicyanin is the key component of a soluble periplasmic electron transfer chain in the bacteriumParacoccus denitrificansthat passes electrons from an amine substrate to a terminal oxidase in the periplasmic membrane. It directly and specifically transfers electrons from methylamine dehydrogenase (MADH) to an inducible c‐type cytochrome,c551i. Amicyanin is a 12.5‐kDa monomeric cupredoxin, MADH is a 124‐kDa heterotetramer oxidizing enzyme, andc551iis a 17.5‐kDa monomeric cytochrome. Crystal structures of amicyanin, a binary MADH–amicyanin complex and a ternary MADH–amicyanin–cytochromec551icomplex, are described and correlated with their kinetic and electron transfer properties in solution.
Copper‐Zinc Superoxide Dismutase in Prokaryotes and Eukaryotes
Authors: Bordo Domenico , Pesce Alessandra , Bolognesi Martino , Elena Stroppolo Maria , Falconi Mattia , Desideri Alessandro 
Published: April 2006

AbstractCu,Zn superoxide dismutases (SODs) are ubiquitous enzymes catalyzing the conversion of superoxide radical anions into O2and H2O2. In eukaryotes, Cu,Zn SOD is a dimeric protein (2 × 16 kDa); each protomer hosts the binuclear Cu,Zn catalytic center. In prokaryotes, Cu,Zn SODs can be monomeric or dimeric, their quaternary structure differing from that of the eukaryotic homologs. The protein tertiary structure (based on an eight‐stranded antiparallel β‐barrel) is conserved through species. Crystal structures and mutational analysis indicate that Cu,Zn SOD activity is based on a redox cycle, whereby the catalytic Cu(II) species is first reduced (to Cu(I)), and then oxidized (back to Cu(II)) by successive encounters with the substrate. The Zn ion plays a key structural role in maintaining active site structural integrity during the catalytic cycle. Efficient electrostatic steering of the anionic substrate to the active site accounts for the very high (diffusion limited) catalytic turnover displayed by all Cu,Zn SODs. Mutations in human cytoplasmic Cu,Zn SOD have been related to the onset of FALS (familial amyotrophic lateral sclerosis , or Lou Gehring disease), a fatal motoneuron degenerative disease.
Catechol Oxidase
Authors: Eicken Christoph , Gerdemann Carsten , Krebs Bernt 
Published: April 2006

AbstractCatechol oxidases are ubiquitous plant enzymes with a dinuclear type‐3 copper center. In the wound‐responsive mechanism of the plant, they catalyze the oxidation of a broad range of o‐diphenols to the corresponding o‐quinones coupled with the reduction of oxygen to water. The crystal structures of catechol oxidase from sweet potato in the resting Cu(II)–Cu(II) state, the reduced Cu(I)–Cu(I) form, and in complex with the inhibitor phenylthiourea were analyzed. The catalytic copper center in a central four‐helix bundle is located in a hydrophobic pocket close to the surface. Both metal sites are coordinated by three histidine ligands. His109, ligated to the CuA site, is covalently linked to Cys92 by an unusual thioether bond. On the basis of biochemical, spectroscopic, and structural data, a catalytic mechanism is proposed in which one of the oxygen atoms of the diphenolic substrate binds to CuB of the oxygenated enzyme. There are close structural relationships of catechol oxidase to different hemocyanins.
Binuclear CopperA
Authors: Kroneck Peter MH 
Published: April 2006

AbstractThe purple CuA is a Cys‐bridged, mixed‐valence electron transfer center [Cu(1.5+)…Cu(1.5+)], found in cytochromecoxidase and in nitrous oxide reductase. More recently, the NO reductase fromBacillus azotoformanswas identified as the third CuA‐containing enzyme. There also exist engineered CuA sites which have been introduced by loop‐directed mutagenesis into blue type 1 copper proteins, such as azurin or amicyanin. Electron transfer mediated by CuA is very efficient. The reasons for utilizing a binuclear electron transfer center in cytochromecoxidase and nitrous oxide reductase, instead of mononuclear type 1 Cu, are suggested to be its unidirectional electron transfer through the site or the lower energy of reorganization. Interest in CuA is directly related to its unique spectroscopic properties. Studies by paramagnetic resonance, magnetic circular dichroism, resonance Raman, and X‐ray absorption spectroscopy have provided a clear picture of the electronic properties of the CuA site and the interaction of the metal atoms with the neighboring amino acids.
Vanadium Haloperoxidases
Authors: Wever Ron , Hemrika Wieger 
Published: April 2006

Abstract
This chapter describes the occurrence and the biological function of the vanadium bromoperoxidases and chloroperoxidases. These enzymes that contain vanadate as the prosthetic group catalyze the oxidation of halides to the corresponding hypohalous acids. Purification and molecular characterization of these enzymes is reported and a detailed comparison is made between a bromoperoxidase and a chloroperoxidase, both kinetically as well as structurally. The vanadate‐binding site in haloperoxidases shows an interesting homology with the binding site of phosphate in a large group of phosphatases. Finally, on the basis of mutagenesis studies, a catalytic mechanism is presented for the vanadium chloroperoxidase activity that details the role in catalysis of the amino acid residues in the first coordination sphere of the metal oxide.