4-Hydroxy-tetrahydrodipicolinate reductase from Neisseria gonorrhoeae - structure and interactions with coenzymes and substrate analog

Abstract

Neisseria gonorrhoeae, an obligate human pathogen, is a leading cause of communicable diseases globally. Due to rapid development of drug resistance, the rate of successfully curing gonococcal infections is rapidly decreasing. Hence, research is being directed toward finding alternative drugs or drug targets to help eradicate these infections. 4-Hydroxy-tetrahydrodipicolinate reductase (DapB), an important enzyme in the meso-diaminopimelate pathway, is a promising target for the development of new antibiotics. This manuscript describes the first structure of DapB from N. gonorrhoeae determined at 1.85 Å. This enzyme uses NAD(P)H as cofactor. Details of the interactions of the enzyme with its cofactors and a substrate analog/inhibitor are discussed. A large scale bioinformatics analysis of DapBs' sequences is also described.

Keywords: 2,6-pyridine dicarboxylic acid; 4-hydroxy-tetrahydrodipicolinate reductase; Dihydrodipicolinate reductase; Lysine biosynthesis; NADH; NADPH.