|
type |
Journal Article |
authors |
Ray, S.S.; Bonanno JB, Rajashankar KR, Pinho MG, He G, De Lencastre H, Tomasz A, Burley S.K. |
title |
Cocrystal structures of diaminopimelate decarboxylase: mechanism, evolution, and inhibition of an antibiotic resistance accessory factor |
journal |
Structure (Camb) |
Activity |
4.1.1.20 |
Family |
4.1.1.20 |
sel |
selected |
ui |
12429091 |
year |
(2002) |
volume |
10 |
number |
11 |
pages |
1499-508 |
| |
keywords |
Carboxy-Lyases/*chemistry/genetics |
abstract |
Cocrystal structures of Methanococcus jannaschii diaminopimelate decarboxylase (DAPDC) bound to a substrate analog, azelaic acid, and its L-lysine product have been determined at 2.6 A and 2.0 A, respectively. This PLP-dependent enzyme is responsible for the final step of L-lysine biosynthesis in bacteria and plays a role in beta-lactam antibiotic resistance in Staphylococcus aureus. Substrate specificity derives from recognition of the L-chiral center of diaminopimelate and a system of ionic "molecular rulers" that dictate substrate length. A coupled-enzyme assay system permitted measurement of kinetic parameters for recombinant DAPDCs and inhibition constants (K(i)) for azelaic acid (89 microM) and other substrate analogs. Implications for rational design of broad-spectrum antimicrobial agents targeted against DAPDCs of drug-resistant strains of bacterial pathogens, such as Staphylococcus aureus, are discussed. |
last changed |
2009/06/08 14:24 |
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