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| - | [[Image:1li0.gif|left|200px]] | + | {{Seed}} |
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| | {{STRUCTURE_1li0| PDB=1li0 | SCENE= }} | | {{STRUCTURE_1li0| PDB=1li0 | SCENE= }} |
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| - | '''Crystal structure of TEM-32 beta-Lactamase at 1.6 Angstrom'''
| + | ===Crystal structure of TEM-32 beta-Lactamase at 1.6 Angstrom=== |
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| - | ==Overview==
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| - | Widespread use of beta-lactam antibiotics has promoted the evolution of beta-lactamase mutant enzymes that can hydrolyze ever newer classes of these drugs. Among the most pernicious mutants are the inhibitor-resistant TEM beta-lactamases (IRTs), which elude mechanism-based inhibitors, such as clavulanate. Despite much research on these IRTs, little is known about the structural bases of their action. This has made it difficult to understand how many of the resistance substitutions act as they often occur far from Ser-130. Here, three IRT structures, TEM-30 (R244S), TEM-32 (M69I/M182T), and TEM-34 (M69V), are determined by x-ray crystallography at 2.00, 1.61, and 1.52 A, respectively. In TEM-30, the Arg-244 --> Ser substitution (7.8 A from Ser-130) displaces a conserved water molecule that usually interacts with the beta-lactam C3 carboxylate. In TEM-32, the substitution Met-69 --> Ile (10 A from Ser-130) appears to distort Ser-70, which in turn causes Ser-130 to adopt a new conformation, moving its O gamma further away, 2.3 A from where the inhibitor would bind. This substitution also destabilizes the enzyme by 1.3 kcal/mol. The Met-182 --> Thr substitution (20 A from Ser-130) has no effect on enzyme activity but rather restabilizes the enzyme by 2.9 kcal/mol. In TEM-34, the Met-69 --> Val substitution similarly leads to a conformational change in Ser-130, this time causing it to hydrogen bond with Lys-73 and Lys-234. This masks the lone pair electrons of Ser-130 O gamma, reducing its nucleophilicity for cross-linking. In these three structures, distant substitutions result in accommodations that converge on the same point of action, the local environment of Ser-130.
| + | The line below this paragraph, {{ABSTRACT_PUBMED_12058046}}, adds the Publication Abstract to the page |
| | + | (as it appears on PubMed at http://www.pubmed.gov), where 12058046 is the PubMed ID number. |
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| | + | {{ABSTRACT_PUBMED_12058046}} |
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| | ==About this Structure== | | ==About this Structure== |
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| | [[Category: Tem-32]] | | [[Category: Tem-32]] |
| | [[Category: X-ray structure]] | | [[Category: X-ray structure]] |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May 2 23:56:25 2008'' | + | |
| | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jul 2 20:57:03 2008'' |
Revision as of 17:57, 2 July 2008
Template:STRUCTURE 1li0
Crystal structure of TEM-32 beta-Lactamase at 1.6 Angstrom
Template:ABSTRACT PUBMED 12058046
About this Structure
1LI0 is a Single protein structure of sequence from Escherichia coli. Full crystallographic information is available from OCA.
Reference
The structural bases of antibiotic resistance in the clinically derived mutant beta-lactamases TEM-30, TEM-32, and TEM-34., Wang X, Minasov G, Shoichet BK, J Biol Chem. 2002 Aug 30;277(35):32149-56. Epub 2002 Jun 10. PMID:12058046
Page seeded by OCA on Wed Jul 2 20:57:03 2008
