Abstract:
:Dihydrofolate and dihydropteroylpolyglutamates inhibit pig liver methylenetetrahydrofolate reductase. In all cases the inhibition is linearly competitive with respect to methylenetetrahydrofolate. The Ki values decrease with each additional glutamyl residue from one to six, from a value of 6.5 microM for dihydrofolate to 0.013 microM for dihydropteroylhexaglutamate. Dihydropteroylheptaglutamate has a Ki of 0.065 microM. These data indicate a free energy of binding of approximately 0.75 kcal/mol for each of the five terminal glutamyl residues in dihydropteroylhexaglutamate. Methylenetetrahydropteroylpolyglutamates are substrates for the enzyme, and the increased free energy of binding is reflected in increased values for Vmax/Km with polyglutamate substrates. Vmax is increased 1.76-fold on going from the mono- to the diglutamate substrate; additional glutamyl residues lead to decreases in Km values for methylenetetrahydropteroylpolyglutamates. Our results suggest that the in vivo activity of methylenetetrahydrofolate reductase may also be sensitive to fluctuations in the ratio of methylenetetrahydropteroylpolyglutamates to dihydropteroylpolyglutamates and that this ratio may be important in determining the relative fluxes of methylenetetrahydropteroylpolyglutamates into the pathways leading to thymidylate biosynthesis and methionine regeneration.
journal_name
Biochemistryjournal_title
Biochemistryauthors
Matthews RG,Baugh CMdoi
10.1021/bi00551a005subject
Has Abstractpub_date
1980-05-13 00:00:00pages
2040-5issue
10eissn
0006-2960issn
1520-4995journal_volume
19pub_type
杂志文章相关文献
BIOCHEMISTRY文献大全abstract::Allosteric activators are generally believed to shift the equilibrium distribution of enzyme conformations to favor a catalytically productive structure; the kinetics of conformational exchange is seldom addressed. Several observations suggested that the usual allosteric mechanism might not apply to the activation of ...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi200785s
更新日期:2011-10-04 00:00:00
abstract::The solution conformation of an agalactosyl penta-antennary "bisected" N-linked glycan from hen ovomucoid has been determined using a combination of 1H-NMR NOE measurements and restrained molecular dynamics (MD) simulations. The majority of glycosidic linkages exhibited restricted torsional fluctuations about the glob...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00043a018
更新日期:1995-10-31 00:00:00
abstract::The guanyl nucleotide binding regulatory protein of retinal rod outer segments, called Gt, that couples the photon receptor rhodopsin with the light-activated cGMP phosphodiesterase, can be resolved into two functional components, alpha t and beta gamma t. The effect of monoclonal antibody binding to the alpha t subun...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00451a047
更新日期:1989-12-12 00:00:00
abstract::To test the prediction that extensively fluorinated (fluorous) proteins should be more stable and exhibit novel self-segregating behavior, the properties of the de novo designed model 4-alpha-helix bundle protein, alpha 4F 6, in which the hydrophobic core is packed entirely with the extensively fluorinated amino acid ...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi702476f
更新日期:2008-04-15 00:00:00
abstract::In human glutathione transferase (GST) A1-1, the C-terminal region covers the active site and contributes to substrate binding. This region is flexible, but upon binding of an active-site ligand, it is stabilized as an amphipatic alpha-helix. The stabilization has implications for the catalytic activity of the enzyme....
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi991482y
更新日期:1999-12-07 00:00:00
abstract::Site-specifically modified oligodeoxynucleotides were used to explore the influence of neighboring base sequence context on the mutagenic potential of N-(deoxyguanosin-8-yl)-2-acetylaminofluorene (dG-AAF) and N-(deoxyguanosin-8-yl)-2-aminofluorene (dG-AF) in mammalian cells. Oligodeoxynucleotides ((5)(')TCCTCCTNXNCTCT...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi0027581
更新日期:2001-03-27 00:00:00
abstract::We have used nucleobase substitution and kinetic analysis to test the hypothesis that hammerhead catalysis occurs by a general acid-base mechanism, in which nucleobases are directly involved in deprotonation of the attacking 2'-hydroxyl group and protonation of the 5'-oxygen that serves as the leaving group in the cle...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi047941z
更新日期:2005-05-31 00:00:00
abstract::We report the use of electrospray ionization (ESI) mass spectrometry (MS) in conjunction with online rapid mixing to monitor the kinetics of acid-induced ferrihemoglobin denaturation. Under equilibrium conditions, the hemoglobin mass spectrum is dominated by the intact heterotetramer. Dimeric and monomeric species are...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi048501a
更新日期:2004-11-23 00:00:00
abstract::An alanine racemase encoded by a gene from the thermophilic Gram-positive bacterium Bacillus stearothermophilus is overproduced to 0.3% of the soluble protein when carried on plasmid pICR4 in Escherichia coli [Inagaki, K., Tanizawa, K., Badet, B., Walsh, C. T., Tanaka, H., & Soda, K. (1986) Biochemistry (third paper o...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00359a029
更新日期:1986-06-03 00:00:00
abstract::We have investigated the binding of a pure H1 histone, the mouse variant H1e, to a 214 bp fragment of DNA from pBR322. Binding was monitored by observing the effects of the protein on melting of the DNA and by a gel-mobility-shift assay. We found, using this highly purified system, that H1e protein binds preferentiall...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00167a049
更新日期:1994-01-11 00:00:00
abstract::Class A beta-lactamases hydrolyze penicillins and other beta-lactams via an acyl-enzyme catalytic mechanism. Ser70 is the active site nucleophile. By constructing the S70A mutant, which is unable to form the acyl-enzyme intermediate, it was possible to make stable ES complexes with various substrates. The stability of...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi9928041
更新日期:2000-05-30 00:00:00
abstract::The transmission of regulatory signals between the alpha- and beta-subunits of the tryptophan synthase alpha 2 beta 2 complex from Salmonella typhimurium has been investigated by monitoring the luminescence properties of the enzyme in the presence and in the absence of the alpha-subunit ligand DL-alpha-glycerol 3-phos...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00148a014
更新日期:1992-08-25 00:00:00
abstract::PHD2 is a 2-oxoglutarate, non-heme Fe(2+)-dependent oxygenase that senses O2 levels in human cells by hydroxylating two prolyl residues in the oxygen-dependent degradation domain (ODD) of HIF1α. Identifying the active site contacts that determine the rate of reaction at limiting O2 concentrations is crucial for unders...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi501540c
更新日期:2015-05-12 00:00:00
abstract::Circular dichroism and difference spectroscopy have been used to study dilute aqueous solutions of oxygenated, deoxygenated, and carbamoylated deoxygenated hemoglobins A and S (HbA and HbS, respectively). The spectra of HbA and HbS, in comparable state of oxygenation or carbamoylation, are identical, strongly implying...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00663a022
更新日期:1976-09-07 00:00:00
abstract::The peptide alpha 1(III)-CB9 was prepared and purified from human liver, and its amino acid sequence was determined. Automated Edman degradation of the intact peptide and peptides derived from selective cleavage with hydroxylamine and digestions with trypsin, thermolysin, and Staph V8 protease enabled determination of...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00512a040
更新日期:1981-04-28 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::Two terminally blocked peptides, acetylAETAAAKFLRQHMamide and acetylAETSSSRYLRQHMamide, were obtained by solid-phase synthesis, purified by reversed-phase chromatography, and characterized by fast atom bombardment mass spectrometry. Both peptides were soluble in aqueous solutions and remained monomeric over the concen...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00427a048
更新日期:1989-01-10 00:00:00
abstract::Guided by the X-ray structure analysis of a crystalline EcoRV-d(GGGATATCCC) complex (Winkler, in preparation), we have begun to identify functionally important amino acid residues of EcoRV. We show here that Asn70, Asp74, Ser183, Asn185, Thr186, and Asn188 are most likely involved in the binding and/or cleavage of the...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00240a011
更新日期:1991-07-02 00:00:00
abstract::Single-strand-specific nucleases are a diverse and important group of enzymes that are able to cleave a variety of DNA structures present in duplex molecules. Nuclease SP, an enzyme from spinach, has been purified to apparent homogeneity, allowing for the unambiguous characterization of a number of its physical proper...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00104a026
更新日期:1991-10-08 00:00:00
abstract::The first step of the kynurenine pathway for l-tryptophan (l-Trp) degradation is catalyzed by heme-dependent dioxygenases, tryptophan 2,3-dioxygenase (TDO) and indoleamine 2,3-dioxygenase. In this work, we employed stopped-flow optical absorption spectroscopy to study the kinetic behavior of the Michaelis complex of C...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/acs.biochem.0c00179
更新日期:2020-08-04 00:00:00
abstract::Esterification of retinol (vitamin A alcohol) with long-chain fatty acids by lecithin-retinol acyltransferase (LRAT) is an important step in both the absorption and storage of vitamin A. Retinol in cells is bound by either cellular retinol binding protein (CRBP), present in most tissues including liver, or cellular re...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00144a014
更新日期:1992-07-28 00:00:00
abstract::An empirical preduction algorithm which uses information on the shrs on either side) interactions in 20 proteins to assign every residue in a protein to one of five conformational states is described. The conformational states are defined in terms of the backbone dihedral angles of the residue so that the prediction a...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00668a030
更新日期:1976-11-16 00:00:00
abstract::Fluorescence lifetimes and fluorescence anisotropy decays of the voltage-sensitive styryl-pyridinium dye RH421 have been measured in the presence of dimyristoylphosphatidylcholine vesicles, the water soluble enzyme ribulose 1,5-bisphosphate carboxylase/oxygenase (rubisco), and Na+,K(+)-ATPase-containing membrane fragm...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00037a015
更新日期:1995-09-19 00:00:00
abstract::Pyruvate phosphate dikinase catalyzes the interconversion of adenosine 5'-triphosphate (ATP), orthophosphate (P(i)), and pyruvate with adenosine 5'-monophosphate (AMP), pyrophosphate (PP(i)), and phosphoenolpyruvate (PEP). The Arg 561 residue of Clostridium symbiosum PPDK is contained within a Gly-rich stretch of sequ...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00007a012
更新日期:1995-02-21 00:00:00
abstract::The present study was carried out to determine the energetics of Clostridium symbiosum pyruvate phosphate dikinase (PPDK) catalyzed interconversion of adenosine 5'-triphosphate (ATP), orthophosphate (Pi), and pyruvate (pyr) with adenosine 5'-monophosphate (AMP), inorganic pyrophosphate, and phosphoenolpyruvate (PEP) [...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00171a007
更新日期:1994-02-08 00:00:00
abstract::Protein prenylation involves the attachment of a hydrophobic isoprenoid moiety to the C-terminus of proteins. Several small GTPases, including members of the Ras and Rho subfamilies, require prenylation for their normal and pathological functions. Recent work has suggested that SmgGDS proteins regulate the prenylation...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/acs.biochem.8b00567
更新日期:2018-07-24 00:00:00
abstract::Steric constraints in the retinal binding pocket of sensory rhodopsin I (SR-I) are analyzed by studying effects of sample temperature and retinal analogs. The flash-induced yield of the earliest detected intermediate S610, which corresponds to the K intermediate in the bacteriorhodopsin (BR) photocycle, decreases belo...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00089a044
更新日期:1993-09-28 00:00:00
abstract::The bleomycins (BLMs), tallysomycins (TLMs), phleomycin, and zorbamycin (ZBM) are members of the BLM family of glycopeptide-derived antitumor antibiotics. The BLM-producing Streptomyces verticillus ATCC15003 and the TLM-producing Streptoalloteichus hindustanus E465-94 ATCC31158 both possess at least two self-resistanc...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/acs.biochem.5b01008
更新日期:2015-11-17 00:00:00
abstract::We studied the basic steps of proton transfer through ATP synthase of chloroplasts, CF0CF1, under conditions of proton slip, a conducting stage in the absence of added nucleotides. On the background of a steady transmembrane pH difference, voltage steps were induced by flashing light. Proton intake, transfer, and rele...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00027a008
更新日期:1995-07-11 00:00:00
abstract::Angiotensin converting enzyme (ACE) plays a critical role in the circulating or endocrine renin-angiotensin system (RAS) as well as the local regulation that exists in tissues such as the myocardium and skeletal muscle. Here we report the high-resolution crystal structures of testis ACE (tACE) in complex with the firs...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi049480n
更新日期:2004-07-13 00:00:00