bluuebunny/crossref_metadata_2025_split huggingface dataset:
DeacetoxycephalosporinCSynthase
Authors: Andersson Inger , Terwisscha van Scheltinga Anke C , Ranghino Graziella , Valegård Karin 
Published: December 2011

AbstractDeacetoxycephalosporin C synthase (DAOCS) is a mononuclear ferrous enzyme, which catalyzes the expansion of the five‐membered thiazolidine ring of the penicillin nucleus into the six‐membered dihydrothiazine ring of the cephalosporin nucleus. The reaction requires dioxygen and 2‐oxoglutarate as co‐substrates to create a reactive iron–oxygen intermediate (a ferryl or peroxo compound) from a ferrous iron in the active site of DAOCS. The extended family of 2‐oxoacid‐dependent ferrous enzymes, to which DAOCS belongs, possesses a common jelly roll β‐barrel fold with the ferrous iron ligated by two histidines and a carboxylate. Here we describe the high‐resolution structures of apo‐DAOCS, and of the enzyme in complex with Fe(II) and co‐substrate 2‐oxoglutarate. On the basis of the structures and the quantum‐chemical calculations, a mechanism is proposed whereby the reactive oxidizing species may be stored in a safe form within the enzyme to await the reaction with the penicillin substrate when it is available.
Iron‐Only Hydrogenases
Authors: Lemon Brian J , Peters John W 
Published: December 2011

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.
Ferritin
Authors: Theil Elizabeth C 
Published: December 2011

AbstractThe ferritin superfamily of protein nanocages oxidizes ferrous ions to form hydrated ferric oxide nanominerals consisting of thousands of iron and oxygen atoms, in a central, internal cavity; varying amounts of phosphate are incorporated. Maxi‐ferritins, found in all eukaryotes and many bacteria and Archea, have diameters of 10–12 nm, constructed from 24 self‐assembling polypeptide subunits (four‐α‐helix bundles) with cavities of ∼8 nm, while mini‐ferritins in bacteria assemble from 12 subunits, are ∼8 nm in diameter, and have cavities of ∼5 nm. Ferritins function in concentrating iron for protein co‐factor synthesis (heme, FeS, etc.), recovering iron during senescence, and trapping excess iron and oxygen; mini‐ferritins, also called Dps proteins, protect bacterial DNA from chemical/physical damage during stress, in some cases binding the DNA in bacterial “chromatin” structures. There are three types of Fe–protein interaction sites in the nanocages, although when mineralized, most of the iron atoms are in the inorganic phase: 1 – catalytic sites, related by simple DNA coding changes to di‐iron oxygenase co‐factors, that couple two ferrous with oxygen atoms into diferric peroxo and ferric oxy/hydroxo mineral precursors; 2 – nucleation sites on the cavity surface that initiate mineral formation; 3 – gated pores at triple subunit junctions, that control access of reductants and chelators to recover the mineral.Genetic regulation of ferritin synthesis is unusually complex, depending both on DNA, and, in animals, on mRNA structures that link ferritin to both antioxidant response proteins (DNA regulation) and iron trafficking proteins (mRNA regulation). The lethality of ferritin gene deletion in animals and the recent demonstration that humans absorb ferritin iron from seeds such as soybeans, illustrate the key role played by ferritins in the normal physiology of iron and oxygen. Exploring ferritin interactions with external cellular components that deliver/remove substrates/products, intra‐cage translocation of oxidation products/mineral precursors and reductants, and the potential use of the protein nanocage in materials or pharmacology are directions for the future.
Lactoferrin
Authors: Smith Clyde A 
Published: December 2011

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.
Methyl‐CoenzymeMReductase
Authors: Grabarse Wolfgang , Shima Seigo , Mahlert Felix , Duin Evert C , Thauer Rudolf K , Ermler Ulrich 
Published: December 2011

AbstractFunctional ClassOccurrenceBiological FunctionAmino Acid Sequence InformationMetal Content and CofactorsProtein Production, Purification, Molecular CharacterizationActivity TestSpectroscopyX‐Ray Structure of InactiveMCRFunctional AspectsFunctional DerivativesPossible Catalytic MechanismAcknowledgementsRelated Articles
Diphtheria Toxin Repressor: Metal Ion Mediated Control of Transcription
Authors: Ringe Dagmar , White Andre , Chen Shuyan , Murphy John R 
Published: December 2011

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.
AminopeptidaseP
Authors: Guss J Mitchell , Freeman Hans C 
Published: December 2011

AbstractAminopeptidase 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 coliaminopeptidase 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: December 2011

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: December 2011

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.
Dissimilatory Nitrate Reductase
Authors: João Romão Maria , Miguel Dias João , Moura Isabel 
Published: December 2011

AbstractThe dissimilatory nitrate reductase (NAP) fromDesulfovibrio desulfuricansATCC 27774 catalyses the reduction of nitrate to nitrite for respiration. It belongs to the DMSO reductase family of molybdoenzymes and contains one single subunit of 755 amino acids with one molybdenum cofactor and one [4Fe–4S] cluster. The Mo atom is coordinated by twocis‐dithiolene groups of two molybdopterin guanine dinucleotides (MGD), by the sulfur atom of Cys140 and by one OH/OH2ligand. One of the MGD cofactors is directly involved in the electron transfer between the molybdenum center and the [4Fe–4S] cluster.
Pseudoazurin
Authors: Adman Elinor T 
Published: December 2011

AbstractPseudoazurin is a small blue copper protein isolated from denitrifying bacteria. Its amino acid sequence and molecular structure are distinct from plastocyanin, azurin, and other members of the cupredoxin family. The Type I Cu center responsible for the intense blue color has copper with 2 His, Cys, and Met ligands in a distorted tetrahedral array. Structures of oxidized and reduced forms of the protein show small, but significant differences. Pseudoazurin transfers electrons to and from nitrite reductase. Site‐directed mutagenesis and other techniques have shown that the likely interaction surface is the hydrophobic surface to which the copper atom is closest, surrounded by positively charged residues that interact with negatively charged counterparts on its electron transfer partners.
Amicyanin and Complexes of Amicyanin with Methylamine Dehydrogenase and Cytochromec551i
Authors: Mathews F Scott 
Published: December 2011

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.
Prokaryotic Copper Amine Oxidases
Authors: McPherson Michael J , Parsons Mark R , Wilmot Carrie M 
Published: December 2011

AbstractFunctional ClassOccurrenceBiological FunctionAmino Acid Sequence InformationProtein Production, Purification and Molecular CharacterizationMetal Content and CofactorsActivity TestSpectroscopyX‐Ray Structures ofCuAOsFunctional AspectsFunctional DerivativesCatalytic MechanismRelated Articles
Galactose Oxidase
Authors: McPherson Michael J , Parsons Mark R , Kate Spooner R , Wilmot Carrie M 
Published: December 2011

AbstractFunctional ClassOccurrenceBiological FunctionAmino Acid Sequence InformationProtein Production, Purification and Molecular CharacterizationMetal Content and CofactorsActivity TestSpectroscopyX‐Ray Structure ofGOFunctional AspectsFunctional DerivativesModel CompoundsCatalytic MechanismRelated Articles
Copper‐Zinc Superoxide Dismutase in Prokaryotes and Eukaryotes
Authors: Bordo Domenico , Pesce Alessandra , Bolognesi Martino , Elena Stroppolo Maria , Falconi Mattia , Desideri Alessandro 
Published: December 2011

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.
Hemocyanins from Arthropods and Molluscs
Authors: Magnus Karen A 
Published: December 2011

AbstractFunctional ClassOccurrenceBiological FunctionAmino Acid Sequence InformationProtein Production, Purifications and Molecular CharacterizationsMetal Content and CofactorsSpectroscopyThree‐Dimensional Structures of Arthropod and Mollusc HemocyaninsFunctional AspectsFunctional DerivativesCooperative MechanismsRelated Articles
Ascorbate Oxidase
Authors: Messerschmidt Albrecht 
Published: December 2011

Abstract

Ascorbate oxidase (AO) is a multicopper oxidase related to laccase and ceruloplasmin. It catalyzes the four‐electron reduction of dioxygen to water with concomitant one‐electron oxidation of the substrate. The most efficient reducing substrate is l‐ascorbate, but several one‐electron reductants may interact with AO. It occurs in higher plants in both vegetative and reproductive organs in the cytoplasm of the cells. The biological function of AO is still unclear. A very attractive function is its involvement in anti‐oxidative defense. AO has been intensively characterized by spectroscopic, kinetic, electrochemical, and X‐ray crystallographic methods. The amino acid sequences have been determined from several plant sources and fungi. The X‐ray structure of AO from zucchini shows that the monomer of 552 residues is built up by three domains arranged sequentially on the polypeptide chain. The folding of all three domains is of a ß‐barrel type. Each monomer has three disulfide bridges. It contains a mononuclear type 1 copper site in domain 3 and a trinuclear type 2/type 3 copper site between domains 1 and 3. The mononuclear copper site has the four canonical type 1 copper ligands (His, Cys, His, Met) also found in plastocyanin and azurin. The trinuclear copper site has eight histidine ligands (symmetrically supplied by domains 1 and 3) and two oxygen ligands. The type 3 copper pair is bridged by an OH
−
or O
2−
. The remaining copper has two histidine ligands and an OH
−
or H
2
O ligand. The average copper–copper distance in oxidized AO is 3.74 Å. The shortest distance between the type 1 copper center and the trinuclear copper center is 12.2 Å. X‐ray structures of the fully reduced, peroxide and azide forms of AO have been determined. In the fully reduced form, the trinuclear site undergoes strong changes. The bridging oxygen ligand is released and the copper–copper distances increase from an average of 3.7 Å to 5.1 Å for the copper pair and to about 4.2 Å from the paired atoms to the third copper atom. In the peroxide form, the peroxide is bound end‐on to one copper atom of the copper pair while two azide molecules are bound in the same fashion to the same copper atom. Spectroscopic and kinetic studies reveal that the entry site for electrons from the reducing substrate is the mononuclear copper and the dioxygen binding site is the trinuclear copper species. The enzyme acts in a ‘two‐site ping‐pong bi‐bi’ mechanism. A proposal for the catalytic mechanism of AO based on the available data is given. Aspects of intramolecular electron transfer are discussed.
Laccase
Authors: Davies Gideon J , Ducros Valérie 
Published: December 2011

AbstractFunctional ClassOccurrenceBiological FunctionAmino Acid Sequence InformationMetal ContentActivity TestsSpectroscopyX‐Ray Structure of LaccaseFunctional AspectsFunctional DerivativesCatalytic MechanismDiscussionAcknowledgementsRelated Articles
Ceruloplasmin
Authors: Lindley Peter F. 
Published: December 2011

AbstractCeruloplasmin is a multi‐copper oxidase that contains most of the copper present in the plasma. It is an acute‐phase reactant that exhibits a two‐ to three‐fold increase over the normal concentration of 300 mg ml−1in adult plasma. However, the precise physiological role(s) of ceruloplasmin has been the subject of intensive debate and it is likely that the enzyme has a multi‐functional role, including iron oxidase activity and oxidation of biogenic amines. The three‐dimensional X‐ray structure of the human enzyme shows that the molecule is composed of six cupredoxin‐type domains arranged in a triangular array. There are six integral copper atoms per molecule (mononuclear sites in domains 2, 4, and 6 and a trinuclear site between domains 1 and 6) and two labile sites with roughly 50% occupancy. Further structural studies on the binding of metal cations by the enzyme have indicated a putative mechanism for ferroxidase activity. Other studies have located the binding sites for an inhibitor (azide) and various substrates [aromatic diamines, biogenic amines, andD‐lysergic acid diethylamide (LSD)]. The binding site of the azide moiety is topologically equivalent to one of the sites reported for ascorbate oxidase. However, there are two distinct binding sites for amine substrates; aromatic diamines bind at the base of domain 4 remote from the mononuclear copper site, whereas the biogenic amine series typified by serotonin, epinephrine, and dopa bind in close vicinity to that site utilized by cations in domain 6 and close to the mononuclear copper.
Vanadium Haloperoxidases
Authors: Wever Ron , Hemrika Wieger 
Published: December 2011

AbstractThis 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.
Xanthine Oxidoreductase
Authors: Nishino Takeshi , Pai Emil F 
Published: December 2011

AbstractA single gene product has been identified as responsible for the two catalytic activities, xanthine dehydrogenase, XDH (EC 1.1.1.204), and xanthine oxidase, XO (EC 1.2.3.2). Synthesized as XDH (ultimate electron acceptor NAD+), the protein can be converted to XO (ultimate electron acceptor oxygen) either reversibly by oxidation of cysteine residues or irreversibly by proteolysis. Xanthine oxidoreductase (XOR) is a ubiquitous enzyme; its physiological role is the oxidation of hypoxanthine to xanthine and further to uric acid, althoughin vitrothe enzyme's specificity is rather broad, accepting a large number of purines, pteridines, and aldehydes as substrates. XOR, in contrast to most other hydroxylases, incorporates water‐derived oxygen into its substrate. The electrons are transferred from xanthine to a Mopterin center and from there via two Fe2–S2clusters and FAD to NAD+or oxygen, respectively. The enzyme is the target of the antigout drug allopurinol; it is involved in hyperuricemia and xanthinuria and postulated to participate in postischemic reperfusion injury. Crystal structures have been determined for native and mutant XDHs and XOs from man, cow, rat, andRhodobacter capsulatus. The conformational changes linked to the dehydrogenase/oxidase transition have been identified and interpreted. A structure‐based explanation for the catalytic mechanism is emerging.
Metal ions in cyanobacterial photosystem I
Authors: Saenger Wolfram , Biesiadka Jacek , Loll Bernhard 
Published: December 2011

AbstractPhotosystems I (PSI) and photosystem II (PSII) are large multi‐subunit protein–cofactor complexes located in the photosynthetic thylakoid membrane and acting in series. They are fueled by sunlight, PSII oxidizing water to atmospheric O2, H+, and electrons that are delivered at the lumenal side of the membrane. The electrons are transferred to PSI where their reducing potential is increased sufficiently to finally produce reduced nicotinamide adenine dinucleotide phosphate (NADPH) at oxidized form of nicotinamide adenine dinucleotide phosphate (NADP+) reductase while the H+form a gradient across the membrane that drives adenosine triphosphate (ATP‐)synthetase and both, NADPH and ATP, convert CO2to carbohydrates in the Calvin cycle.PSI is composed of 12 different protein subunits of which 9 are embedded in the thylakoid membrane and 3 are located on the cytoplasmic (stromal) side of the membrane. Sunlight is absorbed by a large internal antenna composed of 90 chlorophylla(Chla), and the photons are guided to the electron transfer chain (ETC) formed by two symmetry‐related branches where the ‘special pair P 700′ located close to the lumenal side of the membrane is excited and expels an electron to form the cation radical P700+. The electron is guided from P700 to the stromal side along the ETC consisting of pairs of accessory Chla, of the primary electron acceptors (Chla), of the secondary acceptors phylloquinone (PQ), to the terminal acceptors formed by three Fe4S4clusters FX, FA, FB. Since each Chlacoordinates one Mg2+, PSI harbors a plethora of Mg and Fe cations and one structural Ca2+. We describe the coordination of these cations and their function in the photosynthetic process carried out by PSI.