1jwv: Difference between revisions
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|PDB= 1jwv |SIZE=350|CAPTION= <scene name='initialview01'>1jwv</scene>, resolution 1.85Å | |PDB= 1jwv |SIZE=350|CAPTION= <scene name='initialview01'>1jwv</scene>, resolution 1.85Å | ||
|SITE= | |SITE= | ||
|LIGAND= | |LIGAND= <scene name='pdbligand=CB4:PINACOL[[2-AMINO-ALPHA-(1-CARBOXY-1-METHYLETHOXYIMINO)-4-THIAZOLEACETYL]AMINO]METHANEBORONATE'>CB4</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</scene> | ||
|ACTIVITY= [http://en.wikipedia.org/wiki/Beta-lactamase Beta-lactamase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.5.2.6 3.5.2.6] | |ACTIVITY= <span class='plainlinks'>[http://en.wikipedia.org/wiki/Beta-lactamase Beta-lactamase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.5.2.6 3.5.2.6] </span> | ||
|GENE= bla ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=562 Escherichia coli]) | |GENE= bla ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=562 Escherichia coli]) | ||
|DOMAIN= | |||
|RELATEDENTRY= | |||
|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1jwv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1jwv OCA], [http://www.ebi.ac.uk/pdbsum/1jwv PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1jwv RCSB]</span> | |||
}} | }} | ||
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[[Category: Shoichet, B K.]] | [[Category: Shoichet, B K.]] | ||
[[Category: Wang, X.]] | [[Category: Wang, X.]] | ||
[[Category: beta-lactamase]] | [[Category: beta-lactamase]] | ||
[[Category: crystal structure]] | [[Category: crystal structure]] | ||
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[[Category: tem-1]] | [[Category: tem-1]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 21:40:13 2008'' | ||
Revision as of 21:40, 30 March 2008
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| , resolution 1.85Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | , | ||||||
| Gene: | bla (Escherichia coli) | ||||||
| Activity: | Beta-lactamase, with EC number 3.5.2.6 | ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Crystal structure of G238A mutant of TEM-1 beta-lactamase in complex with a boronic acid inhibitor (sefb4)
OverviewOverview
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-->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.
About this StructureAbout this Structure
1JWV is a Single protein structure of sequence from Escherichia coli. Full crystallographic information is available from OCA.
ReferenceReference
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
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