bluuebunny/crossref_metadata_2025_split huggingface dataset:
Fts
H
/
Hfl
B
Authors: Bieniossek Christoph , Baumann Ulrich 
Published: December 2011

Abstract

The ATP‐dependent, membrane‐standing metalloprotease FtsH/HflB (filamentation temperature‐sensitive locus H/high frequency of lysogenisation locus B) is universally conserved in eubacteria, chloroplasts, and mitochondria. Its substrates are integral membrane proteins, for example, it degrades the unassembled subunits such as SecY of the SecYEG translocon or the a‐subunit of F
o
ATPase, as well as some soluble proteins, most notably the heat shock factor σ
32
, the λ‐phage transcriptional activator λ‐CII and LpxC, a key enzyme in lipid A biosynthesis. FtsH is the only essential energy‐dependent protease in
Escherichia coli
and its knockout shows generally severe phenotypes, for example, malfunctioning of paraplegin, a close homolog in human mitochondria, results in one form of spastic paraplegia. The crystal structure of the cytosolic region reported here reveals a self‐compartmentalizing protease composed of two hexameric rings. The protease ring exhibits perfect sixfold symmetry with a novel, virtually all‐helical fold of the monomers. The active center is formed by the
427
HEAGH motif and the conserved Asp500 as third zing ligand. The AAA domains have ADP bound and are arranged in a hexameric ring with twofold symmetry only. Two of the essential pore residues Phe234, which are implied in substrate binding and translocation, are located toward the interior of the two rings. This suggests a mechanism of substrate recognition and unfolding.
Copper Transporters and Chaperones
Authors: Arnesano Fabio , Banci Lucia 
Published: December 2011

AbstractCopper is an essential element for many cellular processes in all the kingdoms of life. Its presence in cells needs to be tightly controlled, as free copper ions can be toxic due to their redox chemistry, though they must be available to obtain the mature form of copper‐dependent proteins.For this purpose, organisms have developed a machinery for proteins, which control copper uptake, transport, sequestration, and efflux. These proteins are engaged in complex, highly specific pathways, responsible for copper incorporation in target proteins, its transport within a compartment and/or through different cellular compartments and organelles, and its excretion. In the present chapter, we describe the structural and functional features of proteins involved in the three most characterized processes, that is, copper delivery to the trans‐Golgi network or transport across the plasma membrane, involving copper‐transporting adenosine triphosphatases, copper incorporation into the Cu,Zn superoxide dismutase, and into the two copper centers of cytochromecoxidase, located in two different enzyme subunits and involving three copper ions.The structural properties of various functional states of these copper transport proteins, and the related mechanisms, are discussed with respect to their key role in cellular processes.
Pyruvate–Ferredoxin Oxidoreductase
Authors: Chabriere Eric , Cavazza Christine , Contreras‐Martel Carlos , Fontecilla‐Camps Juan C. 
Published: December 2011

AbstractPyruvate decarboxylation in many anaerobic organisms is catalyzed by the thiamine diphosphate (ThDP)‐dependent pyruvate–ferredoxin oxidoreductase. We have determined the native structure of this ancient enzyme, as well as of several reaction intermediates, by soaking crystals in a pyruvate‐containing solution. As the reaction progresses, ThDP approaches the substrate and cleaves a CC bond generating an acetyl‐ThDP radical intermediate and CO2. The comparison of this structure with a similar intermediate in transketolase (TK), another ThDP‐dependent enzyme, reveals significant differences in the cofactor conformation.
Indoleamine 2,3‐Dioxygenase and Tryptophan 2,3‐Dioxygenase
Authors: Thackray Sarah J , Bruckmann Chiara , Mowat Christopher G , Forouhar Farhad , Chapman Stephen K , Tong Liang 
Published: December 2011

AbstractIndoleamine 2,3‐dioxygenase (IDO) and tryptophan 2,3‐dioxygenase (TDO) are heme‐containing enzymes from a small family of homologous enzymes. Despite both catalyzing the dioxygenation ofL‐tryptophan, the first step in the kynurenine pathway, the sequence similarity between TDO and IDO is low. Alignment of sequences across this family of enzymes is only possible on the basis of their structures. Human IDO shows activity toward a wider range of substrates than TDO, and is found throughout the body, while TDO is limited to the liver and epidermis in mammals. To date, no functional prokaryotic IDO has been identified, while TDO is found in many bacteria. TDO and IDO have been implicated in a number of human physiological conditions, including suppression of T‐cell proliferation and the immune escape of cancers, making them attractive targets for drug discovery.
Thioredoxin‐Like [2Fe–2S] Ferredoxin
Authors: Meyer Jacques , Andrade Susana LA , Einsle Oliver 
Published: December 2011

AbstractThioredoxin‐like [2Fe–2S] ferredoxin (Trx‐like‐Fd) is a soluble homodimer of ca. 100‐residue subunits, each containing a [2Fe–2S] cluster. This cluster is redox active and shuttles between the diferric [2Fe–2S]2+and the ferric–ferrous mixed‐valence [2Fe–2S]+state. The four cysteine ligands of the cluster occur in an idiosyncratic Cys‐X10, 12‐Cys‐X29, 34‐Cys‐X3‐Cys pattern. The small size of this protein and the tight insertion of the Fe–S cluster within the protein framework suggest an electron transfer function. However, the dimeric structure and the presence of a protruding loop in the vicinity of the Fe–S cluster may be indicative of a regulatory function. Protein folds similar to the Trx‐like‐Fd monomer occur as domains or subunits in many redox enzymes. In these cases, a single copy of the polypeptide chain is present with anN‐terminal extension of ca. 100 residues, and the protruding loop is shorter or absent altogether. Trx‐like‐Fd has been studied in considerable detail by high‐resolution X‐ray crystallography, spectroscopy, and site‐directed mutagenesis. Its function, however, has so far remained unknown.
Calx‐β Domains
Authors: Hilge Mark 
Published: December 2011

AbstractCalx‐β domains that display the architecture of a seven‐stranded β‐sandwich form a relatively new class of Ca2+binding domains and are most closely related to C2 domains. Depending on the presence of a few acidic key residues in their Ca2+binding sites, Calx‐β domains can bind up to four Ca2+ions with affinities ranging from 10−7to 10−4 M. Functionally, the two copies of Calx‐β domains present in the cytosolic loop of the Na+/Ca2+exchanger are most extensively investigated and act as sensors for intracellular Ca2+. However, the physiological role of the vast majority of Calx‐β domains, located in the extracellular matrix, is intriguing since Ca2+concentrations in this environment are generally high.
Nickel Regulatory Transcription Factor,NikR
Authors: Phillips Christine M , Drennan Catherine L 
Published: December 2011

AbstractThe variety of roles that transition metals fulfill within the cell is staggering, but the concentrations of these metals must be tightly regulated to maintain minimal requisite levels and simultaneously prevent metal‐induced oxidative stress or inappropriate metal‐binding events. A variety of bacteria control the concentration of the transition metal nickel using the transcriptional repressor NikR. To suppress the import of nickel, the NikR protein binds nickel ions, inducing NikR's affinity for a promoter region upstream of a gene encoding a nickel‐specific importer. This binding event blocks RNA polymerase from attaching to the DNA, preventing the expression of further nickel‐specific importers. A variety of biochemical, structural, and spectroscopic studies on NikR have provided interesting insight into the overall function and structure of this regulatory protein.
Nonheme Iron Halogenases
Authors: Blasiak Leah C , Drennan Catherine L 
Published: December 2011

Abstract

Nonheme iron halogenases require Fe(II), O
2
, α‐ketoglutarate (αKG), and a halide ion and catalyze halogenation at unactivated, aliphatic carbons on their substrates. The nonheme iron halogenase SyrB2, from

Pseudomonas syringae

, catalyzes chlorination of threonine during biosynthesis of the plant toxin syringomycin. The X‐ray crystal structure of SyrB2 revealed a mononuclear iron center coordinated by two histidine residues, bidentate αKG, and a chloride ion. Spectroscopic studies on the nonheme iron halogenase CytC3 from
Streptomyces
sp. RK95‐74 have implicated an iron(IV)‐oxo as a hydrogen atom abstracting species in a mechanism similar to the related nonheme iron dioxygenases.
Particulate Methane Monooxygenase
Authors: Rosenzweig Amy C 
Published: December 2011

AbstractParticulate methane monooxygenase (pMMO) catalyzes the oxidation of methane to methanol in methanotrophic bacteria. The 300‐kDa pMMO enzyme is a trimeric integral membrane protein, comprising three copies each of three subunits: pmoB, pmoA, and pmoC. Purified pMMO contains both copper and iron, although some of the iron may be due to heme contamination. The copper stoichiometry ranges from 2 to 15 copper ions per 100‐kDa pMMO protomer, depending on the enzyme source. EPR spectra of whole cells, membrane‐bound, and purified pMMO consistently indicate the presence of type 2 Cu(II). According to XAS data, both Cu(I) and Cu(II) are present. EXAFS data reveal the presence of oxygen/nitrogen ligands and a short CuCu interaction at 2.5 Å that increases to 2.6 Å upon chemical reduction. Crystal structures of pMMO from two organisms have been reported. A soluble region consisting of six cupredoxin‐like β‐barrel structures is supported by 15 transmembrane helices. Three different metal centers have been detected crystallographically: a highly conserved dinuclear copper center, a nonconserved mononuclear copper center, and a site that can be occupied by zinc or copper. Although the identity of the pMMO active site remains unknown, some information regarding the mechanism has been obtained from substrate studies and computational work.
The Membrane‐Bound Nitrate Reductase
A
from Escherichia Coli:
Nar
GHI
Authors: Bertero Michela 
Published: December 2011

Abstract

The bacterium

Escherichia coli

is able to survive in a wide range of adverse environmental conditions. When oxygen is limited and nitrate is present,

E. coli

synthesizes a specific electron transfer chain to produce energy for its own survival. The chain is constituted by two membrane‐bound enzymes: the initial formate dehydrogenase FdnGHI and the terminal nitrate reductase NarGHI. Electrons are transferred from the formate oxidation site to the nitrate reduction site with a net translocation of protons across the cytoplasmic membrane. In the recent years, crystallographic studies have shed light on the structure and function of the two enzymes revealing a clear picture of the nitrate electron transfer chain at the atomic level. The present article focuses on the advances obtained on NarGHI, its function and architecture, and the eight redox cofactors that form like an electrical wire through all the enzymes, starting from the electron acceptor site to the catalytic center.
TheCorAMg2+Channel
Authors: Maguire Michael E 
Published: December 2011

AbstractThe CorA Mg2+channel is present in about 50% of bacteria and many archaea. Its ubiquitous eukaryotic homolog is Mrs2, the mitochondrial Mg2+channel. Physiologically, CorA mediates the influx of Mg2+down its electrochemical gradient. It can also mediate the influx of Ni2+and Co2+but only at concentrations that are toxic to the cell. A subclass of the CorA superfamily in the bacteria mediates the efflux of Zn2+. The sequence analysis of the CorA superfamily shows a complete lack of homology to any other protein. The crystal structure of CorA confirms its unique nature. CorA is a homopentamer shaped like a funnel with the stem of the funnel within the membrane. Each monomer has two transmembrane segments at the C terminus. All prokaryotic CorA proteins have the same basic structure. A 250–290 amino acid cytosolic N‐terminal domain is followed by transmembrane segment 1, which is followed by a nine amino acid periplasmic loop. This loop is followed by the transmembrane segment 2. Neither transmembrane segment contains any charged amino acids. The C‐terminal cytosolic tail of CorA is almost always six amino acids in length and contains three or four arginine and/or lysine residues. In the structures currently available, the Mg2+‐conducting pore is formed completely by transmembrane segment 1. The cytosolic domain is formed of a seven‐stranded antiparallel β sheet flanked on both sides by three α helices (α1–3β1–7α4–6). This domain is followed by the 100‐Å‐long α7helix, which forms most of the inner face of the funnel and transmembrane segment 1. In the cytosolic domain, a Mg2+cation is bound between an aspartate residue in the α7helix of one monomer and the α3helix of the adjacent monomer, giving five bound Mg2+cations per channel. These bound ions seem poised to act as ‘sensors’ of intracellular Mg2+, and their dissociation from the channel is proposed to allow the monomers to rotate apart, thus opening the channel.
Hydrophilic Domain of Respiratory ComplexIfromThermus thermophilus
Authors: Sazanov Leonid 
Published: December 2011

AbstractComplex I (NADH:ubiquinone oxidoreductase) plays a central role in cellular energy production, coupling electron transfer between NADH and quinone to proton translocation. It is the largest protein complex of bacterial and mitochondrial respiratory chains. Mitochondrial complex I is a major source of reactive oxygen species (ROS), which may be one of the causes of aging. Dysfunction of the enzyme is implicated in many human neurodegenerative diseases. Complex I is an L‐shaped multisubunit protein assembly consisting of a hydrophilic peripheral arm and a hydrophobic membrane arm. The crystal structure of the hydrophilic domain of complex I fromThermus thermophiluswas solved recently. This subcomplex consists of eight subunits and contains all the redox centers of the enzyme, including nine iron–sulfur clusters. The electron transfer pathway through the enzyme is about 95 Å long, proceeding from the primary electron acceptor flavin mononucleotide through seven conserved iron–sulfur clusters to the quinone‐binding site at the interface with the membrane domain. The structure of the complete enzyme and the coupling mechanism are not yet known.
Iron‐Binding Protein
Fut
A
1
Authors: Koropatkin Nicole , Pakrasi Himadri B , Smith Thomas J 
Published: December 2011

Abstract

FutA1 belongs to the bacterial extracellular solute‐binding protein family 1 and is part of an ATP‐binding cassette‐type (ABC‐type) transport system involved in the uptake of iron. In
Synechocystis
6803, the
futA1
(
slr1295)
and
futA2
(
slr0513
) genes encode periplasmic binding proteins that have been proposed to be part of a high‐affinity iron‐transport system, although these genes, along with those encoding the transmembrane pore and intracellular ATPase proteins, are widely distributed throughout the genome. While the solute‐binding domains in the cluster 9 ABC transport systems have a relatively rigid α‐helix running down the back of the protein, which restricts domain movement, FutA1 has two β‐strands connecting the two domains of the protein. It is likely that these β‐strands permit the large domain movement observed during iron binding and release. In FutA1, iron is chelated by four tyrosine and one histidine residues. These tyrosine residues do not move during the opening and closing of the binding‐site cleft. This is likely due to a strong secondary shell of interacting residues which also improve iron‐tyrosine interactions by increasing the electronegativity of the tyrosine hydroxyls. Unlike a number of other periplasmic iron‐binding proteins, there are no apparent anion interactions with the bound ferric iron.
[
Ni
Fe
] Hydrogenase Maturing Proteins
Hyp
C
,
Hyp
D
,
Hyp
E
Authors: Watanabe Satoshi , Miki Kunio 
Published: December 2011

Abstract

[NiFe] hydrogenases carry an NiFe(CO)(CN)
2
center at the active site, which catalyzes the reversible oxidation of molecular hydrogen. Hyp proteins (HypABCDEF) are required for the maturation of [NiFe] hydrogenase. HypA and HypB are involved in the insertion of the nickel atom. HypE and HypF catalyze the biosynthesis of the cyanide ligand in the form of HypE‐thiocyanate. HypC and HypD are assumed to deliver the iron atom with diatomic ligands to the active site of hydrogenase. The structures of HypC consist of an OB‐fold like β‐barrel domain and C‐terminal one or two α helices. The C‐terminal helices are shown to be quite flexible. The structure of HypE consists of two α/β domains and is similar to other PurM superfamily proteins. The C‐terminal tail of HypE adopts an outward extended conformation in the absence of adenosine 5′ triphosphate (ATP) or an inward closed conformation in the presence of ATP. The structure of HypD is composed of two α/β domains and an Fe–S cluster binding domain. Conserved regions of HypD show its probable iron binding and active sites for cyanation. The [4Fe–4 S] cluster environment of HypD is shown to be quite similar to that of ferredoxin : thioredoxin reductase (FTR). The cyanation reaction can be catalyzed through thiol redox signaling in the HypCDE complex.
para‐AminobenzoateN‐Oxygenase
Authors: Zhao Huimin , Nair Satish K. 
Published: December 2011

AbstractThe monooxygenase AurF catalyzes the oxidation of a primary amine during the biosynthesis of the antibiotic aureothin. Biochemical reconstitution ofin vitroactivity demonstrates that AurF is a nonheme iron‐dependent enzyme. Crystallographic elucidation of the 3D structure reveals homology to the ribonucleotide reductase family of monooxygenases, despite a lack of appreciable similarity in the primary sequence.
4‐Hydroxybenzoyl‐CoenzymeAReductase
Authors: Boll Matthias 
Published: December 2011

AbstractThe dehydroxylating 4‐hydroxybenzoyl‐CoA reductase (HBCR) plays an important role in the degradation ofpara‐hydroxylated aromatic compounds in anaerobic bacteria. The enzyme catalyzes the removal of the phenolic hydroxyl group from 4‐hydroxybenzoyl‐CoA, yielding benzoyl‐CoA and water; a reduced ferredoxin serves as an electron donor. The enzyme belongs to the xanthine oxidase (XO) family of molybdenum cofactor containing enzymes and contains a molybdopterin‐cytosine dinucleotide cofactor, two [2Fe–2S] clusters, FAD and a [4Fe–4S] cluster per functional unit. HBCR is unique among XO family members in catalyzing the irreversible reduction of the substrate. A mechanism that differs from all other XO membersviahighly reactive radical intermediates has been suggested. The structural, electrochemical, spectroscopic, and kinetic properties of HBCR fromThauera aromaticaare highlighted and compared with other members of the xanthine oxidase family.
Hydroxyquinol 1,2‐Dioxygenase
Authors: Briganti Fabrizio , Ferraroni Marta 
Published: December 2011

AbstractHydroxyquinol 1,2‐dioxygenase (1,2‐HQD) is an intradiol dioxygenase that uses a nonheme ferric iron to activate the substrate for an electrophilic attack by molecular oxygen to cleave hydroxyquinol (1,2,4‐trihydroxybenzene) or chlorohydroxyquinols between the vicinal hydroxyls. This enzyme is involved in the aerobic metabolism of chloroaromatic compounds containing two or more chlorine substituents. The article focuses on the structure–function relationship of 1,2‐HQD and the comparison, at the molecular level, of the structural factors responsible for the differential substrate selectivity in known ring‐cleaving intradiol dioxygenases.
Structure, Spectroscopy, and Function of Tyrosinase; Comparison with Hemocyanin and Catechol Oxidase
Authors: Tepper Armand W J W , Lonardi Emanuela , Bubacco Luigi , Canters Gerard W 
Published: December 2011

AbstractThis article deals with tyrosinase, an enzyme that converts monophenols into diphenols and subsequently into orthoquinones with concomitant use of molecular oxygen as the source of oxygen atoms and oxidizing equivalents. The enzyme occurs widespread in nature. Its active center consists of a dinuclear copper site. The occurrence of tyrosinases and their biological function is reviewed. Information about primary (aa sequence, genetic organization), secondary, and tertiary structures is reviewed and, where appropriate, compared with similar information about related proteins with a dinuclear Cu site (hemocyanins, catechol oxidase). Methods to produce and purify tyrosinase are reviewed. Spectroscopic studies (optical; EPR, NMR, EXAFS) are reviewed in relation to the enzyme mechanism, which is discussed at the end of the article.
Peptidylglycine α‐Hydroxylating Monooxygenase (PHM)
Authors: Rudzka Katarzyna , Chufán Eduardo E , Eipper Betty , Mains Richard , Amzel Mario L 
Published: December 2011

AbstractNumerous peptides function as hormones, neurotransmitters, and growth factors. Enzymatic α‐amidation is a biologically important posttranslational modification of the C‐terminus of many of these peptides. This modification alters the biological properties and enhances the stability of the peptides toward digestion by carboxypeptidases. Peptidylglycine α‐hydroxylating monooxygenase (PHM) is an ascorbate and copper‐dependent catalytic domain of an α‐amidating enzyme (peptidylglycine α‐amidating monooxygenase, PAM) that catalyzes the stereospecific hydroxylation of an α‐carbon of a terminal glycine residue, the first step in the amidation reaction. This reaction is followed by cleavage of the glycine N Cα bond, which is carried out by the second PAM catalytic domain, peptidyl‐α‐hydroxyglycine α‐amidating lyase (PAL). Detailed structural studies of PHM revealed that its catalytic core binds two copper ions that support the oxygenation reaction by cycling through Cu(II)/Cu(I) oxidation states. These two Cu ions (CuHand CuM) are located 11 Å apart and are separated by a solvent‐accessible cleft. The monooxygenation reaction requires the two‐electron activation of molecular oxygen, which is achieved by the binding of O2to a single Cu(I) center (CuM). Formation of this complex is dependent upon the presence of a peptidylglycine substrate and a reducing agent (ascorbate). Since the resting state of the enzyme contains two Cu(II) ions, the catalytic reaction requires transfer of two electrons from the reducing agent to the metal centers, and from the reduced copper ions to dioxygen. The reduced oxygen species then carries out the stereospecific hydroxylation of glycine after abstraction of thepro‐Shydrogen from Cα. Although, the structure and function of PHM have been broadly studied, the pathway of its electron transfer, the nature of the metal‐oxygen species, and details of the mechanism are still being investigated.