| pubmed-article:10194346 | rdf:type | pubmed:Citation | lld:pubmed |
| pubmed-article:10194346 | lifeskim:mentions | umls-concept:C0220781 | lld:lifeskim |
| pubmed-article:10194346 | lifeskim:mentions | umls-concept:C1883254 | lld:lifeskim |
| pubmed-article:10194346 | lifeskim:mentions | umls-concept:C1710236 | lld:lifeskim |
| pubmed-article:10194346 | lifeskim:mentions | umls-concept:C0243071 | lld:lifeskim |
| pubmed-article:10194346 | lifeskim:mentions | umls-concept:C0243077 | lld:lifeskim |
| pubmed-article:10194346 | lifeskim:mentions | umls-concept:C1707689 | lld:lifeskim |
| pubmed-article:10194346 | lifeskim:mentions | umls-concept:C0249363 | lld:lifeskim |
| pubmed-article:10194346 | pubmed:issue | 14 | lld:pubmed |
| pubmed-article:10194346 | pubmed:dateCreated | 1999-4-29 | lld:pubmed |
| pubmed-article:10194346 | pubmed:abstractText | Series of substrates derivatives of peptide deformylase were systematically synthesized and studied for their capacities to undergo hydrolysis. Data analysis indicated the requirement for a hydrophobic first side chain and for at least two main chain carbonyl groups in the substrate. For instance, Fo-Met-OCH3 and Fo-Nle-OCH3 were the minimal substrates of peptide deformylase obtained in this study, while positively charged Fo-Nle-ArgNH2 was the most efficient substrate (kcat/Km = 4.5 x 10(5) M-1.s-1). On the basis of this knowledge, 3-mercapto-2-benzylpropanoylglycine (thiorphan), a known inhibitor of thermolysin, could be predicted and further shown to inhibit the deformylation reaction. The inhibition by this compound was competitive and proved to depend on the hydrophobicity at the P1' position. Spectroscopic evidence that the sulfur group of thiorphan binds next to the active site metal ion on the enzyme could be obtained. Consequently, a small thiopseudopeptide derived from Fo-Nle-OCH3 was designed and synthesized. This compound behaved as a competitive inhibitor of peptide deformylase with KI = 52 +/- 5 microM. Introduction of a positive charge to this thiopeptide via addition of an arginine at P2' improved the inhibition constant up to 2.5 +/- 0.5 microM, a value 4 orders of magnitude smaller than that of the starting inhibitors. Evidence that this inhibitor, imino[(5-methoxy-5-oxo-4-[[2-(sulfanylmethyl)hexanoyl]amino]pentyl )am ino]methanamine, binds inside the active site cavity of peptide deformylase, while keeping intact the 3D fold of the protein, was provided by NMR. A fingerprint of the interaction of the inhibitor with the residues of the enzyme was obtained. | lld:pubmed |
| pubmed-article:10194346 | pubmed:language | eng | lld:pubmed |
| pubmed-article:10194346 | pubmed:journal | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:10194346 | pubmed:citationSubset | IM | lld:pubmed |
| pubmed-article:10194346 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
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| pubmed-article:10194346 | pubmed:status | MEDLINE | lld:pubmed |
| pubmed-article:10194346 | pubmed:month | Apr | lld:pubmed |
| pubmed-article:10194346 | pubmed:issn | 0006-2960 | lld:pubmed |
| pubmed-article:10194346 | pubmed:author | pubmed-author:BlanquetSS | lld:pubmed |
| pubmed-article:10194346 | pubmed:author | pubmed-author:MeinnelTT | lld:pubmed |
| pubmed-article:10194346 | pubmed:author | pubmed-author:RagusoAA | lld:pubmed |
| pubmed-article:10194346 | pubmed:author | pubmed-author:PatinyLL | lld:pubmed |
| pubmed-article:10194346 | pubmed:issnType | Print | lld:pubmed |
| pubmed-article:10194346 | pubmed:day | 6 | lld:pubmed |
| pubmed-article:10194346 | pubmed:volume | 38 | lld:pubmed |
| pubmed-article:10194346 | pubmed:owner | NLM | lld:pubmed |
| pubmed-article:10194346 | pubmed:authorsComplete | Y | lld:pubmed |
| pubmed-article:10194346 | pubmed:pagination | 4287-95 | lld:pubmed |
| pubmed-article:10194346 | pubmed:dateRevised | 2006-11-15 | lld:pubmed |
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| pubmed-article:10194346 | pubmed:meshHeading | pubmed-meshheading:10194346... | lld:pubmed |
| pubmed-article:10194346 | pubmed:meshHeading | pubmed-meshheading:10194346... | lld:pubmed |
| pubmed-article:10194346 | pubmed:meshHeading | pubmed-meshheading:10194346... | lld:pubmed |
| pubmed-article:10194346 | pubmed:meshHeading | pubmed-meshheading:10194346... | lld:pubmed |
| pubmed-article:10194346 | pubmed:meshHeading | pubmed-meshheading:10194346... | lld:pubmed |
| pubmed-article:10194346 | pubmed:year | 1999 | lld:pubmed |
| pubmed-article:10194346 | pubmed:articleTitle | Design and synthesis of substrate analogue inhibitors of peptide deformylase. | lld:pubmed |
| pubmed-article:10194346 | pubmed:affiliation | Laboratoire de Biochimie, Département de Chimie et Synthèse Organique, UMR 7654 and 7652 Ecole Polytechnique, Palaiseau, France. titi@botrytis.polytechnique.fr | lld:pubmed |
| pubmed-article:10194346 | pubmed:publicationType | Journal Article | lld:pubmed |
| pubmed-article:10194346 | pubmed:publicationType | Research Support, Non-U.S. Gov't | lld:pubmed |
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