Abstract:
:The enzyme 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS) catalyzes the reaction between shikimate 3-phosphate and phosphoenolpyruvate to form 5-enolpyruvylshikimate 3-phosphate, an intermediate in the shikimate pathway, which leads to the biosynthesis of aromatic amino acids. EPSPS exists in an open conformation in the absence of substrates and/or inhibitors and in a closed conformation when bound to the substrate and/or inhibitor. In the present report, the H/D exchange properties of EPSPS from Mycobacterium tuberculosis ( Mt) were investigated for both enzyme conformations using ESI mass spectrometry and circular dichroism (CD). When the conformational changes identified by H/D exchanges were mapped on the 3-D structure, it was observed that the apoenzyme underwent extensive conformational changes due to glyphosate complexation, characterized by an increase in the content of alpha-helices from 40% to 57%, while the beta-sheet content decreased from 30% to 23%. These results indicate that the enzyme underwent a series of rearrangements of its secondary structure that were accompanied by a large decrease in solvent access to many different regions of the protein. This was attributed to the compaction of 71% of alpha-helices and 57% of beta-sheets as a consequence of glyphosate binding to the enzyme. Apparently, MtEPSPS undergoes a series of inhibitor-induced conformational changes, which seem to have caused synergistic effects in preventing solvent access to the core of molecule, especially in the cleft region. This may be part of the mechanism of inhibition of the enzyme, which is required to prevent the hydration of the substrate binding site and also to induce the cleft closure to avoid entrance of the substrates.
journal_name
Biochemistryjournal_title
Biochemistryauthors
Marques MR,Vaso A,Neto JR,Fossey MA,Oliveira JS,Basso LA,dos Santos DS,de Azevedo Junior WF,Palma MSdoi
10.1021/bi800134ysubject
Has Abstractpub_date
2008-07-15 00:00:00pages
7509-22issue
28eissn
0006-2960issn
1520-4995journal_volume
47pub_type
杂志文章相关文献
BIOCHEMISTRY文献大全abstract::To probe the details of small amplitude motions in proteins, a dynamical analysis of the orientation fluctuations of two tyrosine side chains in the bovine pancreatic trypsin inhibitor is presented. Detailed results are given for the time history and correlation functions obtained for the ring motion from a molecular ...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00573a001
更新日期:1979-03-20 00:00:00
abstract::Insulin-stimulated glucose disposal in skeletal muscle proceeds predominantly through a nonoxidative pathway with glycogen synthase as a rate-limiting enzyme, yet the mechanisms for insulin activation of glycogen synthase are not understood despite years of investigation. Isolation of putative insulin second messenger...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi0508845
更新日期:2005-08-23 00:00:00
abstract::The N-terminal region of alpha-spectrin is responsible for its association with beta-spectrin in a heterodimer, forming functional tetramers. Non-erythroid alpha-spectrin (alphaII-spectrin) has a significantly higher association affinity for beta-spectrin than the homologous erythroid alpha-spectrin (alphaI-spectrin)....
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi8013032
更新日期:2009-01-13 00:00:00
abstract::Betaine-homocysteine S-methyltransferase (BHMT) is a zinc-dependent enzyme that catalyzes the transfer of a methyl group from glycine betaine (Bet) to homocysteine (Hcy) to form dimethylglycine (DMG) and methionine (Met). Previous studies in other laboratories have indicated that catalysis proceeds through the formati...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi049821x
更新日期:2004-05-11 00:00:00
abstract::We have systematically validated the activity and inhibition of a HIV-1 protease (PR) variant bearing 17 mutations (PR(S17)), selected to represent high resistance by machine learning on genotype-phenotype data. Three of five mutations in PR(S17) correlating with major drug resistance, M46L, G48V, and V82S, and five o...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/acs.biochem.6b00012
更新日期:2016-04-26 00:00:00
abstract::The objective of this study was to determine the molecular factors that lead to beta-lactamase inhibitor resistance for the M69V variant in SHV-1 beta-lactamase. With mechanism-based inhibitors, the beta-lactamase forms an acyl-enzyme intermediate that consists of a trans-enamine derivative in the active site. This st...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi060990m
更新日期:2006-10-03 00:00:00
abstract::A modified form of procollagen was extracted with 10 M urea from the skin of lambs with dermatosparaxis, a disease which is produced by a genetic defect in the conversion of procollagen to collagen. The extracts contained little if any alpha1 and alpha2 chains of normal type I collagen, and instead they contained the ...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00658a024
更新日期:1976-06-29 00:00:00
abstract::Stopped-flow measurements of protein fluorescence quenching when methotrexate (MTX) binds to dihydrofolate reductase (isoenzyme II) of Streptococcus faecium (SFDHFR II) analyze as the sum of two differentials: a rapid binding phase and a second phase for which the observed rate constant is independent of methotrexate ...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00339a010
更新日期:1985-08-27 00:00:00
abstract::Alpha-synuclein plays a key role in the pathogenesis of many neurodegenerative diseases. To date, its cellular role has yet to be determined, although it has been proposed to be connected to calcium and G protein-mediated dopamine signaling. Alpha-synuclein is known to bind strongly to model membrane surfaces where it...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi0487140
更新日期:2005-01-18 00:00:00
abstract::The major covalently linked multimolecular D fragments found in plasmic digests of factor XIIIa cross-linked fibrin formed under physiological pH and ionic strength conditions consist of D dimers, D trimers, and D tetramers. These fragments are linked by epsilon-amino-gamma-glutamyllysine bonds in the carboxy-terminal...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00118a040
更新日期:1992-01-28 00:00:00
abstract::High-affinity mu-conotoxin block of skeletal muscle Na+ channels depends on an arginine at position 13 (Arg-13). To understand both the mechanism of toxin interaction and the general structure of its binding site in the channel mouth, we examined by thermodynamic mutant cycle analysis the interaction between the criti...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi9724927
更新日期:1998-03-31 00:00:00
abstract::In Sphingomonas CHY-1, a single ring-hydroxylating dioxygenase is responsible for the initial attack of a range of polycyclic aromatic hydrocarbons (PAHs) composed of up to five rings. The components of this enzyme were separately purified and characterized. The oxygenase component (ht-PhnI) was shown to contain one R...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi0611311
更新日期:2006-10-10 00:00:00
abstract::Understanding the molecular mechanisms of enzyme catalysis and allosteric regulation has been a primary goal of biochemistry for many years. The dynamics of these processes, approached through a variety of kinetic methods, are discussed. The results obtained for many different enzymes suggest that multiple intermediat...
journal_title:Biochemistry
pub_type: 杂志文章,评审
doi:10.1021/bi0260839
更新日期:2002-07-02 00:00:00
abstract::Mutations in human copper-zinc superoxide dismutase (SOD1) cause an inherited form of the fatal neurodegenerative disease amyotrophic lateral sclerosis (ALS). Here, we present structures of the pathogenic SOD1 variants D124V and H80R, both of which demonstrate compromised zinc-binding sites. The disruption of the zinc...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi100314n
更新日期:2010-07-13 00:00:00
abstract::Iron is vital for almost all organisms because of its ability to donate and accept electrons with relative ease. It serves as a cofactor for many proteins and enzymes necessary for oxygen and energy metabolism, as well as for several other essential processes. Mammalian cells utilize multiple mechanisms to acquire iro...
journal_title:Biochemistry
pub_type: 杂志文章,评审
doi:10.1021/bi300752r
更新日期:2012-07-24 00:00:00
abstract::The role of basic residues of the 70-80-loop, Arg(74), Arg(75), and Lys(78) (chymotrypsin numbering) in the catalytic function of activated protein C (APC) was investigated by expressing mutants of protein C in which these residues were replaced with Ala in three separate constructs. Following purification to homogene...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi015899r
更新日期:2002-05-14 00:00:00
abstract::The AT-rich interaction domain (ARID) containing BAF250a is a subunit of the BAF-A class of SWI/SNF chromatin remodeling complexes. The ARID belongs to a family of conserved DNA binding domains found in several eukaryotic proteins; however, its exact contribution to BAF250a function and the mechanism of its DNA bindin...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/acs.biochem.9b00852
更新日期:2020-01-14 00:00:00
abstract::The covalent affinity probe maltosyl isothiocyanate (MITC) has been used previously to identify the glucose transporter of human erythrocytes as a component of band 3. By use of limited proteolysis, the site on the Mr 100 000 protein to which MITC attaches has been localized to a 17 000-dalton region near the center o...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00331a001
更新日期:1985-05-07 00:00:00
abstract::Cerebrovascular deposition of fibrillar 39-42 amino acid amyloid beta-protein (Abeta), a condition known as cerebral amyloid angiopathy (CAA), is a key pathological feature of Alzheimer's disease and related disorders including hereditary cerebral hemorrhage with amyloidosis-Dutch type (HCHWA-D). Severe cases of CAA, ...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi0002840
更新日期:2000-06-27 00:00:00
abstract::Methyl esterification of carboxylic acid residues in intact mouse S49 lymphoma cells was examined, and at least 24 proteins were found to be modified. Cell fractionation revealed that a distinct set of these proteins could be found in each of the four fractions. Nuclei contained 11 methyl-esterified proteins at 12, 15...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00344a053
更新日期:1985-11-05 00:00:00
abstract::Polymerase eta is a member of the Y family of DNA polymerases which is able to bypass thymine dimers efficiently and in a relatively error-free manner. To elucidate the mechanism of dimer bypass, the efficiency of dAMP and pyrene nucleotide insertion opposite the thymine dimer and its N3-methyl derivatives was determi...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi0345687
更新日期:2003-08-12 00:00:00
abstract::The beta-glucosidase from Agrobacterium sp. catalyzes the hydrolysis of beta-glucosides via a covalent alpha-D-glucopyranosyl-enzyme intermediate involving Glu358. Hydrolysis of 2,4-dinitrophenyl beta-D-glucopyranoside by the low activity Glu358Asp mutant of Agrobacterium beta-glucosidase is accompanied by time-depend...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00044a033
更新日期:1995-11-07 00:00:00
abstract::Ligand-induced dimerization of receptor tyrosine kinases (RTKs) modulates a system of linked biochemical reactions, sharply switching the RTK from a quiescent state to an active state that becomes phosphorylated and triggers intracellular signaling pathways. To improve our understanding of this molecular switch, we de...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi701892f
更新日期:2008-04-01 00:00:00
abstract::The interaction between the apoprotein of 6-hydroxy-L-nicotine oxidase from Arthrobacter oxidans and the prosthetic group FAD has been investigated by 13C, 15N, and 31P NMR techniques. The FAD prosthetic group was selectively enriched in 13C and 15N isotopes by adding isotopically labeled riboflavin derivatives to the...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00428a016
更新日期:1989-01-24 00:00:00
abstract::Beta2microglobulin (beta2m) is the major protein component of the fibrillar amyloid deposits isolated from patients diagnosed with dialysis-related amyloidosis (DRA). While investigating the molecular mechanism of amyloid fibril formation by beta2m, we found that the beta2m C-terminal peptide of 28 residues (cbeta2m) ...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi0301486
更新日期:2003-11-25 00:00:00
abstract::We review signaling by reactive oxygen species, which is emerging as a major physiological process. However, among the reactive oxygen species, H(2)O(2) best fulfills the requirements of being a second messenger. Its enzymatic production and degradation, along with the requirements for the oxidation of thiols by H(2)O...
journal_title:Biochemistry
pub_type: 杂志文章,评审
doi:10.1021/bi9020378
更新日期:2010-02-09 00:00:00
abstract::A considerable body of data supports the model that the infectious agent (called a prion) which causes the transmissible spongiform encephalopathies is a replicating polypeptide devoid of nucleic acid. Prions are believed to propagate by changing the conformation of the normal cellular prion protein (PrPc) into an inf...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi982328z
更新日期:1999-03-16 00:00:00
abstract::Escherichia coli cAMP receptor protein (CRP) controls more than 20 genes. There are significant differences in the promoter regions in these genes. Thus, an elucidation of the mechanism of CRP action requires knowledge about the mode of selectivity in these promoters. An earlier study [Heyduk, T., & Lee, J. C. (1990) ...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi952187q
更新日期:1996-01-30 00:00:00
abstract::The involvement of Cl(-) and several other monovalent anions in photosynthetic oxygen evolution was studied using photosystem II membranes depleted of Cl(-) by dialysis. The results of these studies differ significantly from results obtained using other depletion methods. Binding studies with glycerol as a cryoprotect...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi026175y
更新日期:2003-02-25 00:00:00
abstract::Di- and triketone inhibitors of (4-hydroxyphenyl)pyruvate dioxygenase (HPPD) are both effective herbicides and therapeutics. The inhibitory activity is used to halt the production of lipophilic redox cofactors in plants and also in humans to prevent accumulation of toxic metabolic byproducts that arise from specific i...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi049317s
更新日期:2004-06-01 00:00:00