Structural and functional characterization of Staphylococcus aureus dihydrodipicolinate synthase.
Lysine biosynthesis is crucial for cell-wall formation in bacteria. Enzymes involved in lysine biosynthesis are thus potential targets for anti-microbial therapeutics. Dihydrodipicolinate synthase (DHDPS) catalyzes the first step of this pathway. Unlike its homologues, Staphylococcus aureus DHDPS is a dimer both in solution and in the crystal and is not feedback inhibited by lysine. The crystal structure of S. aureus DHDPS in the free and substrate bound forms provides a structural rationale for its catalytic mechanism. The structure also reveals unique conformational features of the S. aureus enzyme that could be crucial for the design of specific non-competitive inhibitors.
Girish
Tavarekere S
TS
Molecular Biophysics Unit, Indian Institute of Science, Bangalore, India.
Sharma
Eshita
E
Gopal
B
B
D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000235:genetics; D018360:Crystallography, X-Ray; D019281:Dimerization; D006836:Hydro-Lyases / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000235:genetics; D008239:Lysine / Q000096:biosynthesis; D008969:Molecular Sequence Data; D011487:Protein Conformation; D013211:Staphylococcus aureus / Q000201:enzymology* / Q000235:genetics
D001426:Bacterial Proteins; D006836:Hydro-Lyases; C020040:4-hydroxy-tetrahydrodipicolinate synthase; D008239:Lysine