10529249

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Predicate	Object
rdf:type	pubmed:Citation
lifeskim:mentions	umls-concept:C0023689, umls-concept:C0043408, umls-concept:C0075804, umls-concept:C0441655, umls-concept:C0486805, umls-concept:C0754504, umls-concept:C1704675, umls-concept:C1711351
pubmed:issue	42
pubmed:dateCreated	1999-11-24
pubmed:abstractText	The six-domain, 2035-amino acid subunit high-molecular weight protein 2 (HMWP2) activates salicylate and two cysteines and loads them covalently on its three carrier protein domains during assembly of the iron-chelating virulence factor, yersiniabactin of the plague bacterium Yersinia pestis. The 1-1382 fragment of HMWP2 (ArCP-Cy1-A), overproduced in Escherichia coli, contains the first three domains: the aryl carrier protein (ArCP) domain, the cysteine specific adenylation domain (A), and the first condensation/cyclization domain (Cy1). The ArCP can be posttranslationally phosphopantetheinylated on Ser52 and then loaded with a salicyl group on the phosphopantetheine (Ppant) thiol by action of the YbtE, a salicyl-AMP ligase. The HMWP2 1-1382 fragment can activate L-cysteine as Cys-AMP. The HMWP2 1383-2035 fragment contains the remaining three domains: two peptidyl carrier proteins (PCP1 and PCP2) separated by a second condensation/cyclization domain (Cy2). Phosphopantetheinylation of the HMWP2 1383-2035 fragment at Ser1439 (PCP1) and Ser1977 (PCP2) facilitates cysteinylation of both thiols by HMWP2 1-1382. When the holo 1-1382 and bis-holo 1383-2035 protein fragments are mixed with ATP, salicylate, and cysteine, four products are slowly released [salicylcysteine (Sal-Cys), (hydroxyphenylthiazolinyl)cysteine (HPT-Cys), HPT-Cys-Cys, and the bisheterocyclic HPTT-Cys], reflecting thiolytic rerouting by cysteine in solution of elongating acyl-S-enzyme intermediates tethered at ArCP, PCP1, and PCP2 carrier protein domains, respectively. Conducting the in trans reconstitution with the S1439A mutant of HMWP2 1383-2035 releases only Sal-Cys, while the S1977A mutant leads to HPT-Cys formation but not HPT-Cys-Cys or HPTT-Cys. These results suggest localization of particular acyl-S-enzyme intermediates to each of the three carrier protein regions and also establish the sequential action of Cy1 and Cy2, with the latter producing the tandem 4,2-bisheterocyclic hydroxyphenylthiazolinylthiazolinyl (HPTT) moiety characteristic of this class of siderophores.
pubmed:grant	http://linkedlifedata.com/resource/pubmed/grant/AI 42736
pubmed:commentsCorrections	http://linkedlifedata.com/resource/pubmed/commentcorrection/10529249
pubmed:language	eng
pubmed:journal	http://linkedlifedata.com/resource/pubmed/journal/0370623
pubmed:citationSubset	IM
pubmed:chemical	http://linkedlifedata.com/resource/pubmed/chemical/Acyl Carrier Protein, http://linkedlifedata.com/resource/pubmed/chemical/Bacterial Outer Membrane Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Bacterial Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Carrier Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Cysteine, http://linkedlifedata.com/resource/pubmed/chemical/Dithiothreitol, http://linkedlifedata.com/resource/pubmed/chemical/Iron-Binding Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Peptide Fragments, http://linkedlifedata.com/resource/pubmed/chemical/Periplasmic Binding Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Phenols, http://linkedlifedata.com/resource/pubmed/chemical/Siderophores, http://linkedlifedata.com/resource/pubmed/chemical/Sulfhydryl Compounds, http://linkedlifedata.com/resource/pubmed/chemical/Thiazoles, http://linkedlifedata.com/resource/pubmed/chemical/yersiniabactin
pubmed:status	MEDLINE
pubmed:month	Oct
pubmed:issn	0006-2960
pubmed:author	pubmed-author:MillerD ADA, pubmed-author:SueTT, pubmed-author:WalshC TCT
pubmed:issnType	Print
pubmed:day	19
pubmed:volume	38
pubmed:owner	NLM
pubmed:authorsComplete	Y
pubmed:pagination	14023-35
pubmed:dateRevised	2011-5-27
pubmed:meshHeading	pubmed-meshheading:10529249-Acyl Carrier Protein, pubmed-meshheading:10529249-Amino Acid Sequence, pubmed-meshheading:10529249-Bacterial Outer Membrane Proteins, pubmed-meshheading:10529249-Bacterial Proteins, pubmed-meshheading:10529249-Carrier Proteins, pubmed-meshheading:10529249-Catalysis, pubmed-meshheading:10529249-Cloning, Molecular, pubmed-meshheading:10529249-Cysteine, pubmed-meshheading:10529249-Dithiothreitol, pubmed-meshheading:10529249-Iron-Binding Proteins, pubmed-meshheading:10529249-Molecular Sequence Data, pubmed-meshheading:10529249-Mutagenesis, Site-Directed, pubmed-meshheading:10529249-Peptide Fragments, pubmed-meshheading:10529249-Periplasmic Binding Proteins, pubmed-meshheading:10529249-Phenols, pubmed-meshheading:10529249-Protein Structure, Tertiary, pubmed-meshheading:10529249-Siderophores, pubmed-meshheading:10529249-Substrate Specificity, pubmed-meshheading:10529249-Sulfhydryl Compounds, pubmed-meshheading:10529249-Thiazoles, pubmed-meshheading:10529249-Yersinia pestis
pubmed:year	1999
pubmed:articleTitle	Tandem heterocyclization activity of the multidomain 230 kDa HMWP2 subunit of Yersinia pestis yersiniabactin synthetase: interaction of the 1-1382 and 1383-2035 fragments.
pubmed:affiliation	Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts 02115, USA.
pubmed:publicationType	Journal Article, Research Support, U.S. Gov't, P.H.S.