Structure of nicotinic acid mononucleotide adenylyltransferase from Bacillus anthracis

• Published in: Acta crystallographica. Section F, Structural biology and crystallization communications Structural biology and crystallization communications, 2008-10, Vol.64 (10), p.893-898
• Main Authors: Lu, Shanyun, Smith, Craig D., Yang, Zhengrong, Pruett, Pamela S., Nagy, Lisa, McCombs, Deborah, DeLucas, Lawrence J., Brouillette, Wayne J., Brouillette, Christie G.
• Format: Article
• Language: English
• Subjects: ADENINES; Amino Acid Sequence; ATP; BACILLUS; Bacillus anthracis; Bacillus anthracis - enzymology; Bacillus anthracis - genetics; Bacterial Proteins - chemistry; Bacterial Proteins - metabolism; BIOSYNTHESIS; Conserved Sequence; CRYSTAL STRUCTURE; CRYSTALLOGRAPHY; DIMERS; DRUGS; ENERGY CONSERVATION, CONSUMPTION, AND UTILIZATION; ENZYMES; ESCHERICHIA COLI; FLEXIBILITY; MATERIALS SCIENCE; Models, Molecular; Molecular Sequence Data; NAD - biosynthesis; Nicotinamide-Nucleotide Adenylyltransferase - chemistry; Nicotinamide-Nucleotide Adenylyltransferase - genetics; Nicotinamide-Nucleotide Adenylyltransferase - metabolism; NICOTINIC ACID; nicotinic acid mononucleotide adenylyltransferase; Protein Conformation; Protein Structure Communications; R FACTORS; RESOLUTION; second virial coefficient; self-interaction chromatography; Sequence Alignment
• ISSN: 1744-3091; 1744-3091
• DOI: 10.1107/S1744309108029102

Nicotinic acid mononucleotide adenylyltransferase (NaMNAT; EC 2.7.7.18) is the penultimate enzyme in the biosynthesis of NAD+ and catalyzes the adenylation of nicotinic acid mononucleotide (NaMN) by ATP to form nicotinic acid adenine dinucleotide (NaAD). This enzyme is regarded as a suitable candidate for antibacterial drug development; as such, Bacillus anthracis NaMNAT (BA NaMNAT) was heterologously expressed in Escherichia coli for the purpose of inhibitor discovery and crystallography. The crystal structure of BA NaMNAT was determined by molecular replacement, revealing two dimers per asymmetric unit, and was refined to an R factor and Rfree of 0.228 and 0.263, respectively, at 2.3 Å resolution. The structure is very similar to that of B. subtilis NaMNAT (BS NaMNAT), which is also a dimer, and another independently solved structure of BA NaMNAT recently released from the PDB along with two ligated forms. Comparison of these and other less related bacterial NaMNAT structures support the presence of considerable conformational heterogeneity and flexibility in three loops surrounding the substrate‐binding area.