1TWI

Crystal structure of Diaminopimelate Decarboxylase from m. jannaschii in co-complex with L-lysine

Summary for 1TWI

• Entry DOI: 10.2210/pdb1twi/pdb
• Related: 1TUF
• Descriptor: Diaminopimelate decarboxylase, PYRIDOXAL-5'-PHOSPHATE, MAGNESIUM ION, ... (5 entities in total)
• Functional Keywords: antibiotic resistance, diaminopimelate decarboxylase, lysine biosynthesis, structural genomics, nysgxrc, t135, psi, protein structure initiative, new york sgx research center for structural genomics, lyase
• Biological source: Methanocaldococcus jannaschii
• Total number of polymer chains: 4
• Total formula weight: 195663.78

Authors

Rajashankar, K.R.,Ray, S.S.,Bonanno, J.B.,Pinho, M.G.,He, G.,De Lencastre, H.,Tomasz, A.,Burley, S.K.,New York SGX Research Center for Structural Genomics (NYSGXRC) (deposition date: 2004-07-01, release date: 2004-07-27, Last modification date: 2023-08-23)

Primary citation

Rajashankar, K.R.,Ray, S.S.,Bonanno, J.B.,Pinho, M.G.,He, G.,De Lencastre, H.,Tomasz, A.,Burley, S.K.
Cocrystal structures of diaminopimelate decarboxylase: mechanism, evolution, and inhibition of an antibiotic resistance accessory factor
Structure, 10:1499-1508, 2002

PubMed 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.

PubMed: 12429091
DOI: 10.1016/S0969-2126(02)00880-8

Experimental method

X-RAY DIFFRACTION (2 Å)