1xnz

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{{STRUCTURE_1xnz| PDB=1xnz | SCENE= }}
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'''Crystal Structure of Mn(II) form of E. coli. Methionine Aminopeptidase in complex with 5-(2-chlorophenyl)furan-2-carboxylic acid'''
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===Crystal Structure of Mn(II) form of E. coli. Methionine Aminopeptidase in complex with 5-(2-chlorophenyl)furan-2-carboxylic acid===
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==Overview==
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Methionine aminopeptidase (MetAP) enzymes require a divalent metal ion such as Mn(II), Fe(II), Co(II), Ni(II), or Zn(II) for its removal of the N-terminal methionine from newly synthesized proteins, but it is not certain which of these ions is most important in vivo. Metalloform-selective MetAP inhibitors could be valuable for defining which metals are physiologically relevant for MetAP activation and could serve as leads for development of new therapeutic agents. We have screened a library of 43 736 small drug-like molecules against Escherichia coli MetAP and identified two groups of potent and highly metalloform-selective inhibitors of the Co(II)-form, and of the Mn(II)-form, of this enzyme. Compound 1 is 790-fold more selective for the Co(II)-form, while compound 4 is over 640-fold more potent toward the Mn(II)-form. The X-ray structure of a di-Mn(II) form of E. coli MetAP complexed with the Mn(II)-form-selective compound 4 was obtained, and it shows that the inhibitor interacts with both Mn(II) ions through the two oxygen atoms of its free carboxylate group. The preferential coordination of the hard (oxygen) donors to Mn(II) may contribute to its superb selectivity toward the Mn(II)-form.
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{{ABSTRACT_PUBMED_15506752}}
==About this Structure==
==About this Structure==
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[[Category: Methionine aminopeptidase]]
[[Category: Methionine aminopeptidase]]
[[Category: Structure]]
[[Category: Structure]]
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Revision as of 01:24, 28 July 2008

Image:1xnz.png

Template:STRUCTURE 1xnz

Crystal Structure of Mn(II) form of E. coli. Methionine Aminopeptidase in complex with 5-(2-chlorophenyl)furan-2-carboxylic acid

Template:ABSTRACT PUBMED 15506752

About this Structure

1XNZ is a Single protein structure of sequence from Escherichia coli. Full crystallographic information is available from OCA.

Reference

Metalloform-selective inhibitors of escherichia coli methionine aminopeptidase and X-ray structure of a Mn(II)-form enzyme complexed with an inhibitor., Ye QZ, Xie SX, Huang M, Huang WJ, Lu JP, Ma ZQ, J Am Chem Soc. 2004 Nov 3;126(43):13940-1. PMID:15506752

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