1li9: Difference between revisions
No edit summary |
No edit summary |
||
| Line 1: | Line 1: | ||
[[Image:1li9.gif|left|200px]] | [[Image:1li9.gif|left|200px]] | ||
<!-- | |||
The line below this paragraph, containing "STRUCTURE_1li9", creates the "Structure Box" on the page. | |||
You may change the PDB parameter (which sets the PDB file loaded into the applet) | |||
or the SCENE parameter (which sets the initial scene displayed when the page is loaded), | |||
or leave the SCENE parameter empty for the default display. | |||
| | --> | ||
| | {{STRUCTURE_1li9| PDB=1li9 | SCENE= }} | ||
}} | |||
'''Crystal structure of TEM-34 beta-Lactamase at 1.5 Angstrom''' | '''Crystal structure of TEM-34 beta-Lactamase at 1.5 Angstrom''' | ||
| Line 29: | Line 26: | ||
[[Category: Shoichet, B K.]] | [[Category: Shoichet, B K.]] | ||
[[Category: Wang, X.]] | [[Category: Wang, X.]] | ||
[[Category: | [[Category: Antibiotic resistance]] | ||
[[Category: | [[Category: Beta-lactamase]] | ||
[[Category: | [[Category: Tem-34]] | ||
[[Category: | [[Category: X-ray structure]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May 2 23:56:55 2008'' | |||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | |||
Revision as of 23:56, 2 May 2008
Crystal structure of TEM-34 beta-Lactamase at 1.5 Angstrom
OverviewOverview
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.
About this StructureAbout this Structure
1LI9 is a Single protein structure of sequence from Escherichia coli. Full crystallographic information is available from OCA.
ReferenceReference
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 Fri May 2 23:56:55 2008