Publication Abstract from PubMed
Bacterial nicotinate mononucleotide adenylyltransferase encoded by the essential gene nadD plays a central role in the synthesis of the redox cofactor NAD(+). The NadD enzyme is conserved in the majority of bacterial species and has been recognized as a novel target for developing new and potentially broad-spectrum antibacterial therapeutics. Here we report the crystal structures of Bacillus anthracis NadD in complex with three NadD inhibitors, including two analogues synthesized in the present study. These structures revealed a common binding site shared by different classes of NadD inhibitors and explored the chemical environment surrounding this site. The structural data obtained here also showed that the subtle changes in ligand structure can lead to significant changes in the binding mode, information that will be useful for future structure-based optimization and design of high affinity inhibitors.
Complexes of bacterial nicotinate mononucleotide adenylyltransferase with inhibitors: implication for structure-based drug design and improvement.,Huang N, Kolhatkar R, Eyobo Y, Sorci L, Rodionova I, Osterman AL, Mackerell AD, Zhang H J Med Chem. 2010 Jul 22;53(14):5229-39. PMID:20578699[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
