Abstract:
:The continued rise of antibiotic-resistant infections coupled with the limited pipeline of new antimicrobials highlights the pressing need for the development of new antibacterial agents. One potential pathway for new agents is de novo purine biosynthesis as studies have shown that bacteria and lower eukaryotes synthesize purines differently than humans. Microorganisms utilize two enzymes, N5-CAIR synthetase and N5-CAIR mutase, to convert 5-aminoimidazole ribonucleotide (AIR) into 4-carboxy-5-aminoimidazole ribonucleotide (CAIR) through the intermediate N5-carboxy-5-aminoimidazole ribonucleotide (N5-CAIR). In contrast, vertebrates directly convert AIR to CAIR via the enzyme AIR carboxylase. A high-throughput screen against N5-CAIR synthetase identified a group of compounds with a 2,3-indolinedione (isatin) core that inhibited the enzyme. While initial studies suggested that isatins inhibited the enzyme by a noncompetitive mechanism, here we show that isatins inhibit N5-CAIR synthetase by a substrate depletion mechanism. Unexpectedly, we found that isatin reacts rapidly and reversibly with the substrate AIR. The rate of the reaction is dependent upon the substituents on the phenyl moiety of isatin, with 5- and 7-bromoisatin being faster than 4-bromoisatin. These studies suggest that care should be taken when exploring isatin compounds because the biological activity could be a result of their reactivity.
journal_name
Biochemistryjournal_title
Biochemistryauthors
Streeter CC,Lin Q,Firestine SMdoi
10.1021/acs.biochem.8b00939subject
Has Abstractpub_date
2019-04-30 00:00:00pages
2260-2268issue
17eissn
0006-2960issn
1520-4995journal_volume
58pub_type
杂志文章相关文献
BIOCHEMISTRY文献大全abstract::The molecular weight of phosphophoryn, an acidic phosphoprotein unique to dentin matrix, has been difficult to determine because of a combination of neutral protease activities in this tissue and the intrinsic high charge density of the molecule. In this study, bovine dentin phosphophoryn (BDPP) was isolated by a proc...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00287a025
更新日期:1983-08-30 00:00:00
abstract::Two new inhibitors in which the terminal α-carboxyl groups of Z-Ala-Ala-Phe-COOH and Z-Ala-Pro-Phe-COOH have been replaced with a proton to give Z-Ala-Ala-Phe-H and Z-Ala-Pro-Phe-H, respectively, have been synthesized. Using these inhibitors, we estimate that for α-chymotrypsin and subtilisin Carlsberg the terminal ca...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi300688k
更新日期:2012-08-07 00:00:00
abstract::X-ray absorption spectra are reported for the multi-Cu oxidase Rhus vernicifera laccase in oxidized and fully reduced forms and for laccase from which the type 2 Cu has been depleted (T2D). The structure of the Cu K edge for both preparations shows the presence of CuII and CuI in the oxidized and reduced states, respe...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00310a008
更新日期:1984-07-17 00:00:00
abstract::Frequency-resolved fluorescence measurements have been performed to quantitate the lateral stress of the lipid layer containing nonbilayer phase preferring dioleoylphosphatidylethanolamine (DOPE). On the basis of a new rotational diffusion model, the wobbling diffusion constant (Dw), the curvature-related hopping diff...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00130a005
更新日期:1992-04-21 00:00:00
abstract::The mechanism of activation of cGMP phosphodiesterase by the GTP-binding protein in the disc membrane of retinal rods has been investigated by measuring the light-induced phosphodiesterase activity in reconstituted systems where the concentration of either the GTP-binding protein or the phosphodiesterase is varied. Th...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00444a040
更新日期:1989-09-05 00:00:00
abstract::The hydrogen-bonded ring NH nuclear magnetic resonance (NMR) spectra of several transfer ribonucleic acid (RNA) species have been examined with particular emphasis on the extreme low-field portion. Betwen --13.8 and --15 ppm there are two extra resonances which are not derived from cloverleaf base pairs. A combined ap...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00585a025
更新日期:1979-09-04 00:00:00
abstract::The calcitonin gene-related peptide (CGRP) receptor is a heterodimer of two membrane proteins: calcitonin receptor-like receptor (CLR) and receptor activity-modifying protein 1 (RAMP1). CLR is a class B G-protein-coupled receptor (GPCR), possessing a characteristic large amino-terminal extracellular domain (ECD) impor...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi901848m
更新日期:2010-03-09 00:00:00
abstract::Avian magnetoreception is assumed to occur in the retina. Although its molecular mechanism is unclear, magnetic field-dependent formation and the stability of radical-containing photointermediate(s) are suggested to play key roles in a hypothesis called the radical pair mechanism. Chicken cryptochrome4 (cCRY4) has bee...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/acs.biochem.0c00495
更新日期:2020-09-29 00:00:00
abstract::Cells cultured from human skin synthesize precursor forms of types I and III collagens. After denaturation and reduction, the polypeptide chains obtained from these molecules had molecular weights estimated to be 140,000 and 120, 000. The larger chains, the pro alpha chains, are believed to be derived from the origina...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00679a007
更新日期:1975-04-22 00:00:00
abstract::The environmentally sensitive fluorescent probes 6-propionyl-2-(N,N-dimethylamino)naphthalene (PRODAN) and 2'-(N,N-dimethylamino)-6-naphthoyl-4-trans-cyclohexanioc acid (DANCA) form complexes with the heme binding site of apohorseradish peroxidase. The dissociation constants of the PRODAN and DANCA complexes were dete...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi951983t
更新日期:1996-01-23 00:00:00
abstract::Ultraviolet irradiation of calmodulin in the presence of calcium results in either the intramolecular cross-linking of Tyr99 and Tyr138 [Malencik, D.A., & Anderson, S.R. (1986) Biochemistry 25, 709] or, when [Tyr8]substance P is bound, the generation of peptide-calmodulin adducts. The latter consist of two chromatogra...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00403a016
更新日期:1988-02-09 00:00:00
abstract::The hepatitis delta virus (HDV) ribozyme and HDV-like ribozymes are self-cleaving RNAs found throughout all kingdoms of life. These RNAs fold into a double-nested pseudoknot structure and cleave RNA, yielding 2',3'-cyclic phosphate and 5'-hydroxyl termini. The active site nucleotide C75 has a pK(a) shifted >2 pH units...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi100670p
更新日期:2010-08-10 00:00:00
abstract::LTbetaR is a member of the TNF receptor family of proteins. It binds to two different cell surface ligands, LIGHT, a homotypic trimer, and LTalpha1beta2, a heterotypic trimer. We have measured the affinities of the dimeric IgG fusion protein, LTbetaRIgG, and monomeric LTbetaR protein binding to both LIGHT and LTalpha1...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi060210+
更新日期:2006-08-22 00:00:00
abstract::Cyanide inhibits the CO oxidation activity of carbon monoxide dehydrogenase from Clostridium thermoaceticum by binding tightly to the form of the C-cluster yielding the gav = 1.82 signal (the C1.82 form). CN- dissociates and the enzyme reactivates upon addition of CO, CO2 plus dithionite, or CS2 plus dithionite. Dithi...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00195a011
更新日期:1994-07-26 00:00:00
abstract::The Escherichia coli cAMP receptor protein (CRP) displays biphasic characteristics in protease and beta-galactosidase induction assays at increasing cAMP concentrations in response to ligand binding at the secondary binding site located between the primary binding site and the DNA binding domain. Two mutants were crea...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi0479609
更新日期:2005-06-21 00:00:00
abstract::Modelin-5 isoforms were used to gain an insight into the effects of amidation on antimicrobial selectivity. When tested against Escherichia coli, amidation increased toxicity 10-fold (MIC = 31.25 μM) while showing limited increased hemolytic activity (2% lysis). Our results show that both the amidated and non-amidated...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi201267v
更新日期:2011-12-20 00:00:00
abstract::Peptidylglycine monooxygenase (PHM) catalyzes the final step in the biosynthesis of amidated peptides that serve as important signaling molecules in numerous endocrine pathways. The catalytic mechanism has attracted much attention because of a number of unique attributes, including the presence of a pair of uncoupled ...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi4015264
更新日期:2014-02-18 00:00:00
abstract::Myosin subfragment 1 (S1) was covalently labeled with a fluorescent dye, N-[7-(dimethylamino)-4-methyl-3-coumarinyl]maleimide (DACM), and then digested by trypsin to cleave S1 heavy chain into fragments. The DACM-labeled and trypsin-treated S1 was complexed with F-actin and treated with a zero-length cross-linker, 1-e...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00262a043
更新日期:1982-09-14 00:00:00
abstract::We describe a real-time assay for the interaction of the G-protein of retinal rods, transducin (Gt), with its effector, cGMP phosphodiesterase (PDE). The purified proteins were recombined with isolated rod disk membranes. Reactions were triggered by flash photolysis of the receptor rhodopsin, and monitored by changes ...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00083a024
更新日期:1993-08-17 00:00:00
abstract::Leucine aminopeptidase (LAP) is a protease requiring two divalent metal cations per subunit for activity. Zn2+, Mg2+, and Co2+ metal-substituted forms of LAP have been prepared and investigated kinetically. Substitution of metal into the two binding sites independently resulted in the preparation of Zn2+Zn2+, Mg2+Zn2+...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00285a010
更新日期:1983-08-02 00:00:00
abstract::The high-frequency resonance Raman spectra of FeIII yeast native cytochrome c peroxidase (CCP) and five of its mutants [CCP(MI), Phe-51, Leu-48, Lys-48, Asn-235, and Phe-191] were recorded in phosphate buffer, pH 7.0, and in glycerol/phosphate mixtures at 295 and 10 K. Glycerol induces heme coordination changes in som...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00438a024
更新日期:1989-06-13 00:00:00
abstract::We have mapped the interface between the two transmembrane alpha-helices in the membrane domain of the Escherichia coli enzyme leader peptidase by analyzing disulfides formed between pairs of cysteine residues introduced near their respective periplasmic ends. The interface is formed primarily from aliphatic amino aci...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00084a020
更新日期:1993-08-24 00:00:00
abstract::Although the binding of various forms of bleomycin to DNA has been studied extensively, the transient nature of the activated bleomycin species which ultimately attacks DNA has largely precluded direct examination of its physical interactions with DNA. In an attempt to map the minimum binding site required for this sp...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi962957d
更新日期:1997-04-08 00:00:00
abstract::Prenyltransferase (EC 2.5.1.1) has been obtained from chicken liver in a stable crystalline form. The enzyme has been shown to be homogeneous by polyacrylamide gel electrophoresis at pH 8.4, and by electrophoresis in sodium dodecyl sulfate containing gels. Electrofocusing of the crystalline enzyme results in a single ...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00672a009
更新日期:1975-01-14 00:00:00
abstract::Glycosaminoglycans (GAGs) have been reported to play a significant role in amyloid formation of a wide range of proteins/peptides either associated with diseases or native biological functions. The exact mechanism by which GAGs influence amyloid formation is not clearly understood. Here, we studied two closely related...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi401398k
更新日期:2013-12-10 00:00:00
abstract::The clathrin assembly protein complex AP-2 is a multimeric subunit complex consisting of two 100-115-kDa subunits known as alpha and beta and 50- and 16-kDa subunits. The subunits have been dissociated and separated by ion-exchange chromatography in 7.5 M urea. Fractions highly enriched in either the alpha or beta sub...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00236a036
更新日期:1991-06-04 00:00:00
abstract::The two distinct domains of flavocytochrome b2 (L-lactate:cytochrome c oxidoreductase, EC 1.1.2.3) are connected by a typical hinge peptide. To probe the importance of the structural integrity of the hinge region for efficient intraprotein electron transfer, three mutant enzymes have been constructed: H delta 3 [Sharp...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi950457z
更新日期:1996-01-23 00:00:00
abstract::We have studied the photoreaction of 8-methoxypsoralen (8-MOP), 4,5',8-trimethylpsoralen (TMP), and 4'-(hydroxymethyl)-4,5',8-trimethylpsoralen (HMT) with a pair of 18-base-long oligonucleotides in which a 14-base region is complementary. Only one 5'TpA site, favored for both monoadduct and cross-link formation with p...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00409a012
更新日期:1988-05-03 00:00:00
abstract::Transcription of the human nonmuscle myosin II heavy chain-A (NMHC-A) gene is regulated via multiple elements located in intron 1, including element F which contains an E-box. In this study we have identified and characterized the factors that are capable of binding to element F. Yeast one-hybrid screening using eleme...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi002847d
更新日期:2001-07-31 00:00:00
abstract::A new approach to studying membrane topology and permissive sites in membrane proteins expressed in Escherichia coli is described. The method is based on in vitro transposition of mini-Tn5 derivatives bearing dual pho-lac reporters [Alexeyev, M. F., and Winkler, H. H. (1999) J. Mol. Biol. 285, 1503-1513]. Two mini-Tn5...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi011813i
更新日期:2002-01-08 00:00:00