3HFJ

Bacillus anthracis nicotinate mononucleotide adenylytransferase (nadD) in complex with inhibitor CID 3289443

Summary for 3HFJ

• Entry DOI: 10.2210/pdb3hfj/pdb
• Descriptor: Nicotinate (Nicotinamide) nucleotide adenylyltransferase, 3-amino-N-(3-fluorophenyl)-6-thiophen-2-ylthieno[2,3-b]pyridine-2-carboxamide, CALCIUM ION, ... (4 entities in total)
• Functional Keywords: enzyme-inhibitor complex, nad, nucleotidyltransferase, pyridine nucleotide biosynthesis, transferase
• Biological source: Bacillus anthracis (anthrax,anthrax bacterium)
• Total number of polymer chains: 2
• Total formula weight: 44710.57

Authors

Zhang, H.,Huang, N.,Eyobo, Y. (deposition date: 2009-05-11, release date: 2009-09-08, Last modification date: 2024-02-21)

Primary citation

Sorci, L.,Pan, Y.,Eyobo, Y.,Rodionova, I.,Huang, N.,Kurnasov, O.,Zhong, S.,MacKerell, A.D.,Zhang, H.,Osterman, A.L.
Targeting NAD biosynthesis in bacterial pathogens: Structure-based development of inhibitors of nicotinate mononucleotide adenylyltransferase NadD.
Chem.Biol., 16:849-861, 2009

PubMed Abstract: The emergence of multidrug-resistant pathogens necessitates the search for new antibiotics acting on previously unexplored targets. Nicotinate mononucleotide adenylyltransferase of the NadD family, an essential enzyme of NAD biosynthesis in most bacteria, was selected as a target for structure-based inhibitor development. Using iterative in silico and in vitro screens, we identified small molecule compounds that efficiently inhibited target enzymes from Escherichia coli (ecNadD) and Bacillus anthracis (baNadD) but had no effect on functionally equivalent human enzymes. On-target antibacterial activity was demonstrated for some of the selected inhibitors. A 3D structure of baNadD was solved in complex with one of these inhibitors (3_02), providing mechanistic insights and guidelines for further improvement. Most importantly, the results of this study help validate NadD as a target for the development of antibacterial agents with potential broad-spectrum activity.

PubMed: 19716475
DOI: 10.1016/j.chembiol.2009.07.006

Experimental method

X-RAY DIFFRACTION (2.02 Å)