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'''PSE-4 CARBENICILLINASE, R234K MUTANT''' | '''PSE-4 CARBENICILLINASE, R234K MUTANT''' | ||
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[[Category: Sanschagrin, F.]] | [[Category: Sanschagrin, F.]] | ||
[[Category: Strynadka, N C.J.]] | [[Category: Strynadka, N C.J.]] | ||
[[Category: | [[Category: Carbenicillinase]] | ||
[[Category: | [[Category: Class a beta-lactamase]] | ||
[[Category: | [[Category: R234k mutant]] | ||
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Revision as of 17:11, 2 May 2008
PSE-4 CARBENICILLINASE, R234K MUTANT
OverviewOverview
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.
About this StructureAbout this Structure
1G6A is a Single protein structure of sequence from Pseudomonas aeruginosa. Full crystallographic information is available from OCA.
ReferenceReference
Insights into the molecular basis for the carbenicillinase activity of PSE-4 beta-lactamase from crystallographic and kinetic studies., Lim D, Sanschagrin F, Passmore L, De Castro L, Levesque RC, Strynadka NC, Biochemistry. 2001 Jan 16;40(2):395-402. PMID:11148033 Page seeded by OCA on Fri May 2 17:11:38 2008