Abstract:
:The full three-dimensional structure of the catalytic domain of human stromelysin-1 (SCD) complexed to a novel and potent, nonpeptidic inhibitor has been determined by nuclear magnetic resonance spectroscopy (NMR). To accurately mimic assay conditions, the structure was obtained in Tris buffer at pH 6.8 and without the presence of organic solvent. The results showed that the major site of enzyme-inhibitor interaction occurs in the S1' pocket whereas portions of the inhibitor that occupy the shallow S2' and S1 pockets remained primarily solvent exposed. Because this relatively small inhibitor could not deeply penetrate stromelysin's long narrow hydrophobic S1' pocket, the enzyme was found to adopt a dramatic fold in the loop region spanning residues 221-231, allowing occupation of the solvent-accessible S1' channel by the enzyme itself. This remarkable conformational fold at the enzyme binding site resulted in constriction of the S1' loop region about the inhibitor. Examination of the tertiary structure of the stromelysin-inhibitor complex revealed few hydrogen-bonding or hydrophobic interactions between the inhibitor and enzyme that can contribute to overall binding energy; hence the resultant compact structure may in part account for the relatively high potency exhibited by this inhibitor.
journal_name
Biochemistryjournal_title
Biochemistryauthors
Li YC,Zhang X,Melton R,Ganu V,Gonnella NCdoi
10.1021/bi981328wsubject
Has Abstractpub_date
1998-10-06 00:00:00pages
14048-56issue
40eissn
0006-2960issn
1520-4995pii
bi981328wjournal_volume
37pub_type
杂志文章相关文献
BIOCHEMISTRY文献大全abstract::Proton nuclear magnetic resonance spectra of human hemoglobins in water reveal several exchangeable protons which are indicators of the quaternary structures of both the liganded and unliganded molecules. A comparison of the spectra of normal human adult hemoglobin with those of mutant hemoglobins Chesapeake (FG4alpha...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00682a036
更新日期:1975-06-03 00:00:00
abstract::We have found a new class of inhibitors of the bacterial bioluminescence reaction, the N,N-diphenylalkylamines and acids. We have studied the action of one of these compounds 2,2-diphenylpropylamine. The amine was competitive with the long-chain aliphatic aldehyde substrate (Ki congruent to 0.1 mM) but caused an incre...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00522a027
更新日期:1981-09-15 00:00:00
abstract::The Synechococcus PCC7942 SmtB is a zinc-responsive transcriptional repressor and a member of the ArsR superfamily of prokaryotic metalloregulatory transcription factors. The mechanism of negative regulation by Zn(II) and other metals as well as the coordination chemistry (stoichiometry, affinity, and specificity) of ...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi001140o
更新日期:2000-09-26 00:00:00
abstract::Ultraviolet (uv)-light-mediated formation of protein-DNA adducts in Chinese hamster cell chromatin was investigated in an attempt to compare chromatin alterations induced in vitro with those observed in vivo. Three independent methods of analysis indicated stable protein-DNA associations: (1) a membrane filter assay w...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00653a019
更新日期:1976-04-20 00:00:00
abstract::Human angiotensin-converting enzyme (ACE) has two homologous domains, the N and C domains, with differing substrate preferences. X-ray crystal structures of the C and N domains complexed with various inhibitors have allowed identification of active site residues that might be important for the molecular basis of this ...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi8002605
更新日期:2008-06-03 00:00:00
abstract::NanGIR1 is a catalytic element inserted in the P6 loop of a group I intron (NanGIR2) in the small subunit rRNA precursor of the protist Naegleria andersoni [Einvik, C., Decatur, W. A., Embley, T. M., Vogt, V. M., and Johansen, S. (1997) RNA 3, 710-720]. It catalyzes site-specific hydrolysis at an internal processing s...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi9718595
更新日期:1997-12-23 00:00:00
abstract::We have examined the C cluster in type II CO dehydrogenase (CODH) from Carboxydothermus hydrogenformans using Ni K-edge X-ray absorption near edge spectroscopy and extended X-ray absorption fine structure (EXAFS) spectroscopy. The enzyme was studied under three conditions: "as-isolated" and after treatment with CO or ...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi036104e
更新日期:2004-07-20 00:00:00
abstract::The aromatic hydroxylation of six pairs of selectively deuterated monosubstituted benzenes was investigated with rat liver microsomes of various induction states. The substrates studied included 3,5-D2C6H3X (1a-6a) and 2,4,6-D3C6H2X (1b-6b), where X = Br, CN, NO2, OCH3, CH3, or Ph, respectively. The deuterium content ...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00308a031
更新日期:1984-06-19 00:00:00
abstract::Plasmids containing a site-specifically incorporated O6-methyl- (m6G), O6-ethyl- (e6G), or O6-benzylguanine (b6G) within the ATG initiation codon of the lacZ' gene were used to transform Escherichia coli that were repair proficient or deficient in one or both of the E. coli O6-alkylguanine-DNA alkyltransferases, the u...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00197a020
更新日期:1994-08-09 00:00:00
abstract::Five previously unknown hemorrhagic proteins, designated hemorrhagic toxins a,b,c,d, and e, were isolated from the venom of the western diamondback rattlesnake (Crotalus atrox). Molecular weights of hemorrhagic toxins a-e were determined to be 68 000, 24 000, 24 000, 24 000, and 25 700, respectively, by sodium dodecyl...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00609a033
更新日期:1978-08-08 00:00:00
abstract::The generation of multiprotein complexes at receptors and adapter proteins is crucial for the activation of intracellular signaling pathways. In this study, we used multiple biochemical and biophysical methods to examine the binding properties of several SH2 and SH3 domain-containing signaling proteins as they interac...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi0357311
更新日期:2004-04-13 00:00:00
abstract::P-Glycoprotein (Pgp) expression in cell lines derived from tumors arising from cells which normally express Pgp can be increased by sodium butyrate and other differentiating agents. Although the Pgp level increased 25-fold after sodium butyrate treatment in SW620 human colon carcinoma cells, the intracellular accumula...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00143a002
更新日期:1992-07-21 00:00:00
abstract::Photoactivated adenylyl cyclases are powerful tools for optogenetics and for investigating signal transduction mechanisms in biological photoreceptors. Because of its large increase in enzyme activity in the light, the BLUF (blue light sensor using flavin adenine dinucleotide)-activated adenylyl cyclase (bPAC) from Be...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi500479v
更新日期:2014-08-12 00:00:00
abstract::Chloroperoxidase is a versatile fungal heme-thiolate protein that catalyzes a variety of one-electron and two-electron oxidations. We report here that the alkylation of an essential histidine residue showed no effect on the one-electron peroxidations but inhibited two-electron oxidations. The pH profiles of different ...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi7022656
更新日期:2008-03-04 00:00:00
abstract::We have recently reported that the Na pump alpha-subunit has cytosolic-oriented oligosaccharides which were sensitive to cleavage by an enzyme specific for hydrolysis of N-linked glycans [Pedemonte et al. (1990) Proc. Natl. Acad. Sci. U.S.A. 87, 9789-9793]. We now describe experiments that characterize the saccharides...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00158a008
更新日期:1992-11-03 00:00:00
abstract::Understanding the mechanisms of free energy transfer in metabolism is fundamental to understanding how the chemical forces that sustain the molecular organization of the cell are distributed. Recent studies of molecular motors (1-3) and ATP-driven proton transport (4-6) describe how chemical potential is transferred a...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi025953j
更新日期:2002-07-02 00:00:00
abstract::The three-dimensional conformation of a 24-nucleotide variant of the RNA binding sequence for the coat protein of bacteriophage R17 has been analyzed using NMR, molecular dynamics, and energy minimization. The imino proton spectrum is consistent with base pairing requirements for coat protein binding known from bioche...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00019a030
更新日期:1995-05-16 00:00:00
abstract::Arginase is a binuclear Mn(2+) metalloenzyme that catalyzes the hydrolysis of L-arginine to L-ornithine and urea. X-ray crystal structures of arginase complexed to substrate analogues N(omega)-hydroxy-L-arginine and N(omega)-hydroxy-nor-L-arginine, as well as the products L-ornithine and urea, complete a set of struct...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi002318+
更新日期:2001-03-06 00:00:00
abstract::Sulfolobus solfataricus P2 DNA polymerase IV (Dpo4) is a thermostable archaeal enzyme and a member of the error-prone and lesion-bypass Y-family. In this paper, for the first time, the fidelity of a Y-family polymerase, Dpo4, was determined using pre-steady-state kinetic analysis of the incorporation of a single nucle...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi0357457
更新日期:2004-02-24 00:00:00
abstract::In the course of measuring the concentrations of retinoic acids (RA) in bovine plasma, a major peak was observed which comigrated with 9-cis-RA on normal-phase high-performance liquid chromatography. Rechromatography of this retinoic on reverse-phase high-performance liquid chromatography showed that it was distinct f...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00004a013
更新日期:1995-01-31 00:00:00
abstract::The interactions of Pr(III) and Eu(III) with specifically nitrated derivatives of the basic bovine pancreatic trypsin inhibitor have been studied using optical spectroscopy and nuclear magnetic resonance (NMR) at 250 and 270 MHz. Stability constants for proton and metal binding to nitrotyrosines 10 and 21 determined o...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00623a015
更新日期:1977-02-22 00:00:00
abstract::In a family of proteins, often the three-dimensional structure has been experimentally determined only for one member or a few members of the family. Homology modeling can be used to model the structures of all other members of the family and thus allow comparison of these structures. This approach was applied to hete...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi026729x
更新日期:2002-12-10 00:00:00
abstract::Factors which influence the accessibility, or exposure, of the carbohydrate head group of the glycolipid galactosylceramide (GalCer) at the membrane surface have been examined in lipid model membranes using the technique of galactose oxidase-tritiated sodium borohydride labeling. Both the ceramide composition of GalCe...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00072a016
更新日期:1993-06-01 00:00:00
abstract::The peptide hormone bradykinin exerts important biological functions by binding to and activating bradykinin B2 receptors. B2 receptors belong to the seven transmembrane domain (7TM) receptor family. Cloning of the cDNA sequences for the rat, human, and mouse bradykinin B2 receptor revealed several in-frame AUG triple...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi9601060
更新日期:1996-06-11 00:00:00
abstract::Polyhydroxybutyrate (PHB) synthases catalyze the conversion of beta-hydroxybutyryl coenzyme A (HBCoA) to PHB. These enzymes require an active site cysteine nucleophile for covalent catalysis. A protein BLASTp search using the Class III Chromatium vinosum synthase sequence reveals high homology to prokaryotic lipases w...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi9928086
更新日期:2000-04-11 00:00:00
abstract::Troponin T (TnT) is an essential element in the thin filament-based regulatory system of striated muscle. Alternative mRNA splicing generates multiple TnT isoforms with primary structural differences in the NH2-terminal region. The functional significance of this hypervariable NH2-terminal domain and the developmental...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi9812322
更新日期:1998-10-13 00:00:00
abstract::Previously we showed that the low-molecular-weight mucin (MG2, encoded by MUC7), a major component of human submandibular/sublingual saliva, is a bacterial receptor that coats the tooth surface. Here we tested the hypothesis that the structure of its carbohydrate residues contains important information about its funct...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi972612a
更新日期:1998-04-07 00:00:00
abstract::The phosphorylating of the lysine-rich histone at various stages in the cell cycle has been studied. In rapidly dividing cell populations the lysine-rich histone is phosphorylated rapidly after synthesis and more slowly once bound to the chromosome. The half-life of hydrolysis of such interphase phosphorylation in 5 h...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00682a033
更新日期:1975-06-03 00:00:00
abstract::l-Aspartate oxidase, encoded by the nadB gene, is the first enzyme in the de novo synthesis of NAD+ in bacteria. This FAD-dependent enzyme catalyzes the oxidation of l-aspartate to generate iminoaspartate and reduced flavin. Distinct from most amino acid oxidases, it can use either molecular oxygen or fumarate to reox...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/acs.biochem.7b00307
更新日期:2017-08-08 00:00:00
abstract::A recently discovered bifunctional antibiotic-resistance enzyme named AAC(3)-Ib/AAC(6')-Ib', from Pseudomonas aeruginosa, catalyzes acetylation of aminoglycoside antibiotics. Since both domains are acetyltransferases, each was cloned and purified for mechanistic studies. The AAC(3)-Ib domain appears to be highly speci...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi700111z
更新日期:2007-05-01 00:00:00