1jwp
From Proteopedia
| Line 1: | Line 1: | ||
| - | [[Image:1jwp.jpg|left|200px]] | + | [[Image:1jwp.jpg|left|200px]] |
| - | + | ||
| - | '''Structure of M182T mutant of TEM-1 beta-lactamase''' | + | {{Structure |
| + | |PDB= 1jwp |SIZE=350|CAPTION= <scene name='initialview01'>1jwp</scene>, resolution 1.75Å | ||
| + | |SITE= | ||
| + | |LIGAND= <scene name='pdbligand=PO4:PHOSPHATE ION'>PO4</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] | ||
| + | |GENE= bla ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=562 Escherichia coli]) | ||
| + | }} | ||
| + | |||
| + | '''Structure of M182T mutant of TEM-1 beta-lactamase''' | ||
| + | |||
==Overview== | ==Overview== | ||
| Line 7: | Line 16: | ||
==About this Structure== | ==About this Structure== | ||
| - | 1JWP is a [ | + | 1JWP is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1JWP OCA]. |
==Reference== | ==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:[http:// | + | 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:[http://www.ncbi.nlm.nih.gov/pubmed/12079336 12079336] |
[[Category: Beta-lactamase]] | [[Category: Beta-lactamase]] | ||
[[Category: Escherichia coli]] | [[Category: Escherichia coli]] | ||
| Line 24: | Line 33: | ||
[[Category: tem-1]] | [[Category: tem-1]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 12:09:33 2008'' |
Revision as of 10:09, 20 March 2008
| |||||||
| , resolution 1.75Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | |||||||
| Gene: | bla (Escherichia coli) | ||||||
| Activity: | Beta-lactamase, with EC number 3.5.2.6 | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Structure of M182T mutant of TEM-1 beta-lactamase
Overview
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 Structure
1JWP 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 Thu Mar 20 12:09:33 2008
