Abstract:
:During catalysis by liver alcohol dehydrogenase (ADH), a water bound to the catalytic zinc is replaced by the oxygen of the substrates. The mechanism might involve a pentacoordinated zinc or a double-displacement reaction with participation by a nearby glutamate residue, as suggested by studies of human ADH3, yeast ADH1, and some other tetrameric ADHs. Zinc coordination and participation of water in the enzyme mechanism were investigated by X-ray crystallography. The apoenzyme and its complex with adenosine 5'-diphosphoribose have an open protein conformation with the catalytic zinc in one position, tetracoordinated by Cys-46, His-67, Cys-174, and a water molecule. The bidentate chelators 2,2'-bipyridine and 1,10-phenanthroline displace the water and form a pentacoordinated zinc. The enzyme-NADH complex has a closed conformation similar to that of ternary complexes with coenzyme and substrate analogues; the coordination of the catalytic zinc is similar to that found in the apoenzyme, except that a minor, alternative position for the catalytic zinc is ∼1.3 Å from the major position and closer to Glu-68, which could form the alternative coordination to the catalytic zinc. Complexes with NADH and N-1-methylhexylformamide or N-benzylformamide (or with NAD+ and fluoro alcohols) have the classical tetracoordinated zinc, and no water is bound to the zinc or the nicotinamide rings. The major forms of the enzyme in the mechanism have a tetracoordinated zinc, where the carboxylate group of Glu-68 could participate in the exchange of water and substrates on the zinc. Hydride transfer in the Michaelis complexes does not involve a nearby water.
journal_name
Biochemistryjournal_title
Biochemistryauthors
Plapp BV,Savarimuthu BR,Ferraro DJ,Rubach JK,Brown EN,Ramaswamy Sdoi
10.1021/acs.biochem.7b00446subject
Has Abstractpub_date
2017-07-18 00:00:00pages
3632-3646issue
28eissn
0006-2960issn
1520-4995journal_volume
56pub_type
杂志文章相关文献
BIOCHEMISTRY文献大全abstract::The selective reaction of SH containing proteins and peptides with NTCB (2-nitro-5-thiocyanobenzoic acid) has been reported (Degani, Y., & Patchornick, A. (1974) Biochemistry 13, 1; Jacobson, G.A., Schaffer, M.H., Stark, G.R., & Vanaman, T.C. (1973) J. Biol. Chem. 248, 6583). With this reagent, cysteinyl peptide bonds...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00618a022
更新日期:1978-12-12 00:00:00
abstract::p-Hydroxyphenylpyruvate dioxygenase (HPD) plays a key role in the normal catabolism of tyrosine. An Fe2+/oxygen-dependent enzyme, it converts p-hydroxyphenylpyruvate into homogentisate and is part of the superfamily of alpha-ketoglutarate-dependent enzymes that couples oxidative decarboxylation of an alpha-ketoacid co...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi035762w
更新日期:2004-01-27 00:00:00
abstract::Substrates homoprotocatechuate (HPCA) and O(2) bind to the Fe(II) of homoprotocatechuate 2,3-dioxygenase (FeHPCD) in adjacent coordination sites. Transfer of an electron(s) from HPCA to O(2) via the iron is proposed to activate the substrates for reaction with each other to initiate aromatic ring cleavage. Here, rapid...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi201436n
更新日期:2011-11-29 00:00:00
abstract::The removal of damaged bases by DNA glycosylases is thought to be effectively irreversible, because of an overall equilibrium that favors hydrolysis over synthesis of the N-glycosyl bond. Surprisingly, human alkyladenine DNA glycosylase (AAG) can make damaged DNA by catalyzing formation of an N-glycosyl bond between 1...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi101380d
更新日期:2010-10-26 00:00:00
abstract::N-Ethylmaleimide modified heavy meromyosin in only 3-fold activated by actin rather than 200-fold as is normal heavy meromyosin (Silverman, R., Eisenberg, E., and Kielley, W. W. (1972), Nature (London) 240, 207). Ultracentrifuge studies demonstrated that in the absence of ATP the N-ethylmaleimide modified heavy merom...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00688a020
更新日期:1975-08-26 00:00:00
abstract::Subfragment 1 (S1) prepared from rabbit skeletal muscle myosin was digested with trypsin to cleave the 95K heavy chain into three pieces, i.e., the 23K, 50K, and 20K fragments. The trypsin-treated S1 was then cross-linked with p-nitrophenyl iodoacetate. The cross-linker bridged one of the reactive thiols (SH2) in the ...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00408a045
更新日期:1988-04-19 00:00:00
abstract::Cytochrome c oxidase contains four redox-active metal centers: two heme irons, cytochromes a and a3, and two copper ions, CuA and CuB. Due to the paucity of spectroscopic signatures for both copper sites in cytochrome c oxidase, the ligands and structures for these sites have remained ambiguous. The specific depletion...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00382a005
更新日期:1987-04-21 00:00:00
abstract::The Staphylococcus aureus sortase transpeptidase SrtA isoform is responsible for the covalent attachment of virulence and colonization-associated proteins to the bacterial peptidoglycan. SrtA utilizes two substrates, undecaprenol-pyrophosphoryl-MurNAc(GlcNAc)-Ala-D-isoGlu-Lys(epsilon-Gly(5))-D-Ala-D-Ala (branched Lipi...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi035920j
更新日期:2004-02-17 00:00:00
abstract::We have examined the DNA damage produced by reaction of peroxyl radicals with human fibroblast DNA. DNA damage consisted of both strand breaks and base modifications. The extent of strand breaks and base modifications induced as a function of peroxyl radical concentration was determined by quantitation of fragment siz...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi9918994
更新日期:1999-12-14 00:00:00
abstract::The reaction center protein D1 in photosystem II shows a high turnover during illumination. The degradation of the D1 protein is preceded by photoinhibition of the electron transport in photosystem II. There are two distinct mechanisms for this: acceptor-side- and donor-side-induced photoinhibition. Here, donor-side-i...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi960083p
更新日期:1996-06-18 00:00:00
abstract::Although point mutations usually lead to minor localized changes in protein structure, replacement of conserved Pro-76 with Gly in iso-2-cytochrome c induces a major conformational change. The change in structure results from mutation-induced depression of the pK for transition to an alkaline conformation with altered...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00451a043
更新日期:1989-12-12 00:00:00
abstract::Information on the secondary structure and interactions of RNA is important to understand the biological function of RNA as well as in applying RNA as a tool for therapeutic purposes. Recently, the isoenergetic microarray mapping method was developed to improve the prediction of RNA secondary structure. Herein, for th...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi200463p
更新日期:2011-09-06 00:00:00
abstract::We have examined proteins containing the DNA-binding domain of c-Myb with biophysical methods. This DNA-binding domain consists of three imperfect repeats (R1, R2, and R3) conserved among many species. Our results indicate that the DNA-binding domain forms unspecific and specific complexes with oligodeoxynucleotides. ...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00252a026
更新日期:1994-12-06 00:00:00
abstract::Phospholipids and sterols play multiple roles in cells. In addition to establishing barriers between compartments, they also provide the matrix for assembly and function of a large variety of catalytic processes. Lipid composition is a highly regulated feature of biological membranes, yet its implications for membrane...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/acs.biochem.8b00326
更新日期:2018-07-17 00:00:00
abstract::Serine hydroxymethyltransferase (SHMT) catalyzes the reversible conversion of l-serine and tetrahydrofolate into glycine and 5,10-methylenetetrahydrofolate. This enzyme, which plays a pivotal role in one-carbon metabolism, is involved in cancer metabolic reprogramming and is a recognized target of chemotherapy interve...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/acs.biochem.8b01074
更新日期:2018-12-26 00:00:00
abstract::Despite significant progress in the elucidation of the genetic basis of early-onset familial Alzheimer's disease (AD), the etiology of sporadic cases remains elusive. Although certain genetic loci play a role in conferring susceptibility in some sporadic AD cases, it is likely that the etiology is multifactorial; henc...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi000029f
更新日期:2000-05-23 00:00:00
abstract::Pyruvate dehydrogenase kinase 2 (PDK2) activity is enhanced by the dihydrolipoyl acetyltransferase core (E2 60mer) that binds PDK2 and a large number of its pyruvate dehydrogenase (E1) substrate. With E2-activated PDK2, K(+) at approximately 90 mM and Cl(-) at approximately 60 mM decreased the K(m) of PDK2 for ATP and...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi049488x
更新日期:2004-10-26 00:00:00
abstract::The reversible decline of the nicotinic acetylcholine receptor's response to acetylcholine during prolonged exposure to acetylcholine is known as desensitization. Here, we studied ethanol's modulation of fast agonist-induced desensitization of the nicotinic acetylcholine receptor in postsynaptic membrane vesicles from...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00197a009
更新日期:1994-08-09 00:00:00
abstract::The symmetric, tandem GU mismatch motifs, and , which only differ in the mismatch order, have an average difference in thermodynamic stability of 2 kcal/mol at 37 degrees C. Thermodynamic studies of duplexes containing these motifs indicate the effect is largely localized to the mismatches and adjacent base pairs. The...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi970122c
更新日期:1997-07-01 00:00:00
abstract::The kinetics of reduction of free flavin semiquinones of the individual components of 1:1 covalent and electrostatic complexes of yeast ferric and ferryl cytochrome c peroxidase and ferric horse cytochrome c have been studied. Covalent cross-linking between the peroxidase and cytochrome c at low ionic strength results...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00406a029
更新日期:1988-03-22 00:00:00
abstract::The near-ultraviolet circular dichroism (CD) of three homogeneous anti-type III pneumococcal antibodies in the absence and the presence of the specific hexasaccharide ligand was studied. In addition recombinations and hybridizations of H and L chains derived from two of these antibodies were carried out and the CD spe...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00695a013
更新日期:1975-12-02 00:00:00
abstract::Myosin belongs to the family of motor proteins. Its interaction with actin coupled with hydrolysis of ATP is the molecular basis of muscle contraction. The head segment of myosin, called subfragment 1 (S1), contains the distinct binding sites for ATP and actin and responsible for the ATPase activity. The rate-limiting...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi952565r
更新日期:1996-04-09 00:00:00
abstract::The Stk1/Stp1 and GraSR signal-transduction pathways are two distinct pathways in Staphylococcus aureus that rely on a reversible phosphorylation process in transducing external stimuli intracellularly. Stk1/Stp1 is an eukaryote-like Ser/Thr kinase phosphatase pair involved in purine biosynthesis, cell-wall metabolism...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi401177n
更新日期:2013-11-12 00:00:00
abstract::The 2.15 A resolution crystal structure of arginase from Plasmodium falciparum, the parasite that causes cerebral malaria, is reported in complex with the boronic acid inhibitor 2(S)-amino-6-boronohexanoic acid (ABH) (K(d) = 11 microM). This is the first crystal structure of a parasitic arginase. Various protein const...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi100390z
更新日期:2010-07-06 00:00:00
abstract::Eicosanoids have been implicated in the regulation of arterial smooth muscle cell (SMC) cholesteryl ester (CE) metabolism. These eicosanoids, which include prostacyclin (PGI2), stimulate CE hydrolytic activities. High-density lipoproteins (HDL), which promote cholesterol efflux, also stimulate PGI2 production, suggest...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00459a033
更新日期:1990-02-20 00:00:00
abstract::Human DNA primase synthesizes short RNA primers that DNA polymerase alpha then elongates during the initiation of all new DNA strands. Even though primase misincorporates NTPs at a relatively high frequency, this likely does not impact the final DNA product since the RNA primer is replaced with DNA. We used an extensi...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi9019516
更新日期:2010-02-02 00:00:00
abstract::Tissue factor pathway inhibitor (TFPI) from different cell lines shows up to 15-fold differences in the ratio of anticoagulant to chromogenic activity. The anticoagulant activity was dependent on the purification procedure used and it was possible to isolate two fractions of recombinant TFPI. Only one of these fractio...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00107a002
更新日期:1991-10-29 00:00:00
abstract::The selectivity of binding of Escherichia coli RNA polymerase holoenzyme to a promoter-containing fragment of T7 DNA has been investigated over a range of solution conditions by using a double-label nitrocellulose filter binding assay. A 32P-labeled HaeIII restriction fragment of T7 D111 DNA containing the A1 and D pr...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00556a014
更新日期:1980-07-22 00:00:00
abstract::Group VIA phospholipase A(2) (iPLA(2)beta) is expressed in phagocytes, vascular cells, pancreatic islet beta-cells, neurons, and other cells and plays roles in transcriptional regulation, cell proliferation, apoptosis, secretion, and other events. A bromoenol lactone (BEL) suicide substrate used to study iPLA(2)beta f...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi060502a
更新日期:2006-05-23 00:00:00
abstract::Eukaryotic initiation factor 5 (eIF5) plays multiple roles in translation initiation. Its N-terminal domain functions as a GTPase-activator protein (GAP) for GTP bound to eIF2, while its C-terminal region nucleates the interactions between multiple translation factors, including eIF1, which acts to inhibit GTP hydroly...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi052387u
更新日期:2006-04-11 00:00:00