1jwv

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[[Image:1jwv.jpg|left|200px]]
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{{Seed}}
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{{STRUCTURE_1jwv| PDB=1jwv | SCENE= }}
{{STRUCTURE_1jwv| PDB=1jwv | SCENE= }}
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'''Crystal structure of G238A mutant of TEM-1 beta-lactamase in complex with a boronic acid inhibitor (sefb4)'''
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===Crystal structure of G238A mutant of TEM-1 beta-lactamase in complex with a boronic acid inhibitor (sefb4)===
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==Overview==
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Pressured by antibiotic use, resistance enzymes have been evolving new activities. Does such evolution have a cost? To investigate this question at the molecular level, clinically isolated mutants of the beta-lactamase TEM-1 were studied. When purified, mutant enzymes had increased activity against cephalosporin antibiotics but lost both thermodynamic stability and kinetic activity against their ancestral targets, penicillins. The X-ray crystallographic structures of three mutant enzymes were determined. These structures suggest that activity gain and stability loss is related to an enlarged active site cavity in the mutant enzymes. In several clinically isolated mutant enzymes, a secondary substitution is observed far from the active site (Met182--&gt;Thr). This substitution had little effect on enzyme activity but restored stability lost by substitutions near the active site. This regained stability conferred an advantage in vivo. This pattern of stability loss and restoration may be common in the evolution of new enzyme activity.
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The line below this paragraph, {{ABSTRACT_PUBMED_12079336}}, adds the Publication Abstract to the page
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(as it appears on PubMed at http://www.pubmed.gov), where 12079336 is the PubMed ID number.
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{{ABSTRACT_PUBMED_12079336}}
==About this Structure==
==About this Structure==
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[[Category: Serine hydrolase]]
[[Category: Serine hydrolase]]
[[Category: Tem-1]]
[[Category: Tem-1]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May 2 22:01:29 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jul 28 13:20:37 2008''

Revision as of 10:20, 28 July 2008

Image:1jwv.png

Template:STRUCTURE 1jwv

Crystal structure of G238A mutant of TEM-1 beta-lactamase in complex with a boronic acid inhibitor (sefb4)

Template:ABSTRACT PUBMED 12079336

About this Structure

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

Reference

Evolution of an antibiotic resistance enzyme constrained by stability and activity trade-offs., Wang X, Minasov G, Shoichet BK, J Mol Biol. 2002 Jun 28;320(1):85-95. PMID:12079336

Page seeded by OCA on Mon Jul 28 13:20:37 2008

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