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| {{STRUCTURE_1g6a| PDB=1g6a | SCENE= }} | | {{STRUCTURE_1g6a| PDB=1g6a | SCENE= }} |
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| '''PSE-4 CARBENICILLINASE, R234K MUTANT'''
| | ===PSE-4 CARBENICILLINASE, R234K MUTANT=== |
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| ==Overview==
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| PSE-4 is a class A beta-lactamase produced by strains of Pseudomonas aeruginosa and is highly active for the penicillin derivative carbenicillin. The crystal structure of the wild-type PSE-4 carbenicillinase has been determined to 1.95 A resolution by molecular replacement and represents the first structure of a carbenicillinase published to date. A superposition of the PSE-4 structure with that of TEM-1 shows a rms deviation of 1.3 A for 263 Calpha atoms. Most carbenicillinases are unique among class A beta-lactamases in that residue 234 is an arginine (ABL standard numbering scheme), while in all other class A enzymes this residue is a lysine. Kinetic characterization of a R234K PSE-4 mutant reveals a 50-fold reduction in k(cat)/K(m) and confirms the importance of Arg 234 for carbenicillinase activity. A comparison of the structure of the R234K mutant refined to 1.75 A resolution with the wild-type structure shows that Arg 234 stabilizes an alternate conformation of the Ser 130 side chain, not seen in other class A beta-lactamase structures. Our molecular modeling studies suggest that the position of a bound carbenicillin would be shifted relative to that of a bound benzylpenicillin in order to avoid a steric clash between the carbenicillin alpha-carboxylate group and the conserved side chain of Asn 170. The alternate conformation of the catalytic Ser 130 in wild-type PSE-4 may be involved in accommodating this shift in the bound substrate position.
| | The line below this paragraph, {{ABSTRACT_PUBMED_11148033}}, adds the Publication Abstract to the page |
| | (as it appears on PubMed at http://www.pubmed.gov), where 11148033 is the PubMed ID number. |
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| | {{ABSTRACT_PUBMED_11148033}} |
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| ==About this Structure== | | ==About this Structure== |
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| [[Category: Class a beta-lactamase]] | | [[Category: Class a beta-lactamase]] |
| [[Category: R234k mutant]] | | [[Category: R234k mutant]] |
| ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May 2 17:11:38 2008'' | | |
| | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 1 04:41:29 2008'' |
