Abstract:
:Modification of acyl carrier proteins (ACP) or domains by the covalent binding of a 4'-phosphopantetheine (4'-PP) moiety is a fundamental condition for activation of fatty acid synthases (FASes) and polyketide synthases (PKSes). Binding of 4'-PP is mediated by 4' phosphopantetheinyl transfersases (PPTases). Mycobacterium tuberculosis (Mtb) possesses two essential PPTases: acyl carrier protein synthase (Mtb AcpS), which activates the multidomain fatty acid synthase I (FAS I), and Mtb PptT, an Sfp-type broad spectrum PPTase that activates PKSes. To date, it has not been determined which of the two Mtb PPTases, AcpS or PptT, activates the meromycolate extension ACP, Mtb AcpM, en route to the production of mycolic acids, the main components of the mycobacterial cell wall. In this study, we tested the enzymatic activation of a highly purified Mtb apo-AcpM to Mtb holo-AcpM by either Mtb PptT or Mtb AcpS. By using SDS-PAGE band shift assay and mass spectrometry analysis, we found that Mtb PptT is the PPTase that activates Mtb AcpM. We measured the catalytic activity of Mtb PptT toward CoA, using an activation assay of a blue pigment synthase, BpsA (a nonribosomal peptide synthase, NRPS). BpsA activation by Mtb PptT was inhibited by Mtb apo-AcpM through competition for CoA, in accord with Mtb AcpM activation. A structural model of the putative interaction between Mtb PptT and Mtb AcpM suggests that both hydrophobic and electrostatic interactions stabilize this complex. To conclude, activation of Mtb AcpM by Mtb PptT reveals a potential target of the multistep mycolic acid biosynthesis.
journal_name
Biochemistryjournal_title
Biochemistryauthors
Zimhony O,Schwarz A,Raitses-Gurevich M,Peleg Y,Dym O,Albeck S,Burstein Y,Shakked Zdoi
10.1021/bi501444esubject
Has Abstractpub_date
2015-04-14 00:00:00pages
2360-71issue
14eissn
0006-2960issn
1520-4995journal_volume
54pub_type
杂志文章相关文献
BIOCHEMISTRY文献大全abstract::Proteolytic fragments of bovine testis calmodulin were obtained by limited proteolysis with trypsin or thrombin. Cadmium-113 NMR studies showed that the tryptic fragment encompassing Ca2+ binding domains III and IV (TR2C) gave rise to a spectrum identical with that of the native protein. Two thrombic fragments contain...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00279a001
更新日期:1983-05-10 00:00:00
abstract::A wide variety of biological processes including differentiation, regeneration, and cancer progression are regulated by shedding of membrane-anchored proteins. One of the major sheddases is A Disintegrin And Metalloprotease-17 (ADAM17) whose extracellular region consists of a pro-, a catalytic, a disintegrin-, and a m...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/acs.biochem.5b00497
更新日期:2015-09-29 00:00:00
abstract::Indolicidin is an antimicrobial cationic peptide with broad-spectrum activity isolated from bovine neutrophils. An indolicidin analogue CP-11, ILKKWPWWPWRRK-NH(2), with improved activity against Gram-negative bacteria had increased positive charge and amphipathicity while maintaining the short length of the parent mol...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi035643g
更新日期:2003-12-09 00:00:00
abstract::RS1, also known as retinoschisin, is an extracellular discoidin domain-containing protein that has been implicated in maintaining the cellular organization and synaptic structure of the vertebrate retina. Mutations in the gene encoding RS1 are responsible for X-linked retinoschisis, a retinal degenerative disease char...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi800938g
更新日期:2008-09-02 00:00:00
abstract::Matrix metalloproteinase-13 (MMP-13) is important in the pathology of osteoarthritis (OA). Although MMP-13 is considered a therapeutic target for OA, it is unclear how MMP-13 activity is regulated by the system that comprises various proteinases and their inhibitors. MMP-13 neutralizing antibodies could be a useful to...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi301228d
更新日期:2012-11-06 00:00:00
abstract::The DNA binding domain (DBD) of p53 folds by a complex mechanism that involves parallel pathways and multiple intermediates, both on- and off-pathway. This heterogeneity renders DBD particularly susceptible to misfolding and aggregation. The origins of parallel folding mechanisms are not well understood. DBD folding h...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi062106y
更新日期:2007-03-13 00:00:00
abstract::NADH:ubiquinone oxidoreductase (complex I) from bovine heart mitochondria is a highly complicated, energy transducing, membrane-bound enzyme. It contains 46 different subunits and nine redox cofactors: a noncovalently bound flavin mononucleotide and eight iron-sulfur clusters. The mechanism of complex I is not known. ...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi051809x
更新日期:2006-01-10 00:00:00
abstract::Excluded volume and viscosity effects of crowding agents that mimic crowded conditions in vivo on "classical" burst phase folding kinetics of cytochrome c are assessed in vitro. Upon electron transfer-triggered folding of reduced cytochrome c, far-UV time-resolved circular dichroism (TRCD) is used to monitor folding u...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi301324y
更新日期:2012-12-11 00:00:00
abstract::Histidinol-phosphate aminotransferase (HspAT) is a key enzyme on the histidine biosynthetic pathway. HspAT catalyzes the transfer of the amino group of L-histidinol phosphate (Hsp) to 2-oxoglutarate to form imidazole acetol phosphate (IAP) and glutamate. Thus, HspAT recognizes two kinds of substrates, Hsp and glutamat...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi002769u
更新日期:2001-04-17 00:00:00
abstract::Hexose-1-phosphate uridylyltransferase catalyzes the interconversion of UDP-galactose and glucose-1-P with UDP-glucose and galactose-1-P by a double-displacement mechanism through a covalent intermediate (E-UMP), in which UMP is bonded to one of two histidine residues at the active site, H164 or H166. To identify whic...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00499a003
更新日期:1990-11-27 00:00:00
abstract::Transient contacts between denatured polypeptide chains are likely to play an important part in the initial stages of protein aggregation and fibrillation. To analyze the nature of such contacts, we have carried out a protein engineering study of the 102-residue protein U1A, which aggregates transiently in the wild-ty...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi048509k
更新日期:2004-10-19 00:00:00
abstract::A 39/34-kilodalton (kDa) monomeric dispase fragment of von Willebrand factor (vWF) has been purified by heparin affinity chromatography. Detailed structural analysis of the individual 39- and 34-kDa fragments indicated that they had identical amino acid sequences extending from Leu-480/Val-481 to Gly-718 with an intra...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00447a010
更新日期:1989-10-17 00:00:00
abstract::Many DNA polymerases select their natural substrates, deoxy- as opposed to ribonucleoside triphosphates, with a selectivity greater than 10000-fold. The function of a highly conserved residue, Tyr416, in the palm domain of the parental enzyme, an exo(-) derivative of RB69 DNA polymerase (gp43), a member of the pol alp...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi0202171
更新日期:2002-08-13 00:00:00
abstract::Substitution of Co(II) for the catalytic site Zn(II) of horse liver alcohol dehydrogenase (LADH) yields an active enzyme derivative, CoIIE, with characteristic Co(II) charge-transfer and d-d electronic transitions that are sensitive to the events which take place during catalysis [Koerber, S. C., MacGibbon, A. K. H., ...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00377a031
更新日期:1987-02-10 00:00:00
abstract::The crystal structure of fiddler crab collagenase complexed with the dimeric serine protease inhibitor ecotin at 2.5 A resolution reveals an extended cleft providing binding sites for at least 11 contiguous substrate residues. Comparison of the positions of nine intermolecular main chain hydrogen bonding interactions ...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi9617522
更新日期:1997-05-06 00:00:00
abstract::Expression of the Tn21 mercury-resistance (mer) locus is controlled by the merR gene product, which represses mer structural gene (merTPCAD) transcription in the absence of mercuric ion [Hg(II)] and activates it in the presence of Hg(II). In vivo DNA methylation of the mer regulatory region (merOP) shows that, with or...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00493a011
更新日期:1990-10-16 00:00:00
abstract::The sequence of events involved in poly(ethylene glycol)-mediated fusion of small unilamellar vesicles (SUVs) has been studied. Fusion events were monitored using light scattering for vesicle aggregation, the fluorescence lifetime of membrane probe lipids (DPHpPC and NBD-PS) for membrane mixing, the aqueous fluorescen...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi970404c
更新日期:1997-05-27 00:00:00
abstract::In the presence of Ca2+ norchlorpromazine isothiocyanate forms a monocovalent complex with calmodulin: CAPP1-calmodulin (Newton et al, 1983). Trypsin digestion of [3H]CAPP1-calmodulin yields as the major radioactive peptide N epsilon-CAPP-Lys-Met-Lys, corresponding to residues 75-77 of calmodulin. Stoichiometric amoun...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00435a019
更新日期:1989-05-02 00:00:00
abstract::We have developed a homogeneous time-resolved fluorescence resonance energy transfer (FRET)-based assay that detects the formation of HIV-1 integrase (IN) dimers. The assay utilizes IN monomers that express two different epitope tags that are recognized by their respective antibodies, coupled to distinct fluorophores....
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi101504w
更新日期:2011-03-15 00:00:00
abstract::The signaling apparatus that controls bacterial chemotaxis is composed of a core complex containing chemoreceptors, the histidine autokinase CheA, and the coupling protein CheW. Site-specific spin labeling and pulsed dipolar ESR spectroscopy (PDS) have been applied to investigate the structure of a soluble ternary com...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi100055m
更新日期:2010-05-11 00:00:00
abstract::The Ndi1 enzyme found in the mitochondrial membrane of Saccharomyces cerevisiae is an NDH-2-type alternative NADH-quinone oxidoreductase. As Ndi1 is expected to be a possible remedy for complex I defects of mammalian mitochondria, a detailed biochemical characterization of the enzyme is needed. To identify the ubiquin...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi100005j
更新日期:2010-04-06 00:00:00
abstract::The reaction of enantiomerically pure (2S)-N-acetyl-L-alanyl-L-phenylalanyl alpha-chloroethane with gamma-chymotrypsin was studied as a probe of the mechanism of inactivation of serine proteases by peptidyl chloroalkanes. It was determined crystallographically that the peptidyl chloroethane alkylates His57 with retent...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00250a033
更新日期:1994-11-22 00:00:00
abstract::The bacterial chemoreceptor complex governs signal detection and the upstream elements of chemotactic behavior, but the detailed molecular mechanism is still unclear. We have assembled nativelike functional arrays of an aspartate receptor cytoplasmic fragment (CF) with its two cytoplasmic protein partners (CheA and Ch...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/acs.biochem.6b00234
更新日期:2016-07-05 00:00:00
abstract::By exposing photosystem II (PSII) samples to an incrementing number of excitation flashes at room temperature, followed by freezing, we could compare the Mn-derived multiline EPR signal from the S2 oxidation state as prepared by 1, 5, 10, and 25 flashes of light. While the S2 multiline signals exhibited by these sampl...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi026848c
更新日期:2003-03-11 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::Reactivation of tetrameric porcine skeletal muscle lactic dehydrogenase after dissociation and extensive unfolding of the monomers by 6 M guanidine hydrochloride (Gdn . HCl) is characterized by sigmoidal kinetics, indicating a complex mechanism involving rate-limiting folding and association steps. For analysis of the...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00260a007
更新日期:1982-08-17 00:00:00
abstract::Helicobacter pylori NikR (HpNikR) is a nickel-responsive transcription factor. In addition to a role in nickel homeostasis, HpNikR is proposed to serve as a master activator-repressor for H. pylori acid adaptation by directly or indirectly regulating the expression of a battery of genes. One potential mechanism of thi...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi801742r
更新日期:2009-03-24 00:00:00
abstract::The class C serine beta-lactamase of Enterobacter cloacae P99 was inhibited by a series of aryl methylphosphonate monoester monoanions. The effectiveness of these inhibitors was promoted by an acylamido substituent on the methyl group and a good leaving group at phosphorus. The former preference suggests that noncoval...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00140a024
更新日期:1992-06-30 00:00:00
abstract::We describe a fluorescence assay that can be used to monitor helicase-catalyzed unwinding of duplex DNA continuously in real time. The assay is based on the observation that fluorescence resonance energy transfer (FRET) occurs between donor (fluorescein) and acceptor (hexachlorofluorescein) fluorophores that are in cl...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00251a044
更新日期:1994-11-29 00:00:00
abstract::Escherichia coli 16S RNA from 30S ribosomal subunits was isolated, oxidized at the 3' end, and labeled with the thiosemicarbazide derivatives of fluorescein or eosin. Labeled 16S RNA was reconstituted into 30S subunits. They were almost fully active compared to 30S subunits reconstituted from unlabeled 16S RNA by usin...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00521a033
更新日期:1981-09-01 00:00:00