1LW7

NADR PROTEIN FROM HAEMOPHILUS INFLUENZAE

Summary for 1LW7

• Entry DOI: 10.2210/pdb1lw7/pdb
• Descriptor: TRANSCRIPTIONAL REGULATOR NADR, SULFATE ION, NICOTINAMIDE-ADENINE-DINUCLEOTIDE (3 entities in total)
• Functional Keywords: nad, nmn, nmn adenylyl transferase, ribosylnicotinamide kinase, transferase
• Biological source: Haemophilus influenzae
• Cellular location: Cell membrane; Peripheral membrane protein: P44308
• Total number of polymer chains: 1
• Total formula weight: 44761.06

Authors

Singh, S.K.,Kurnasov, O.V.,Chen, B.,Robinson, H.,Grishin, N.V.,Osterman, A.L.,Zhang, H. (deposition date: 2002-05-30, release date: 2002-08-07, Last modification date: 2024-10-16)

Primary citation

Singh, S.K.,Kurnasov, O.V.,Chen, B.,Robinson, H.,Grishin, N.V.,Osterman, A.L.,Zhang, H.
Crystal structure of Haemophilus influenzae NadR protein. A bifunctional enzyme endowed with NMN adenyltransferase and ribosylnicotinimide kinase activities.
J.Biol.Chem., 277:33291-33299, 2002

PubMed Abstract: Haemophilus influenzae NadR protein (hiNadR) has been shown to be a bifunctional enzyme possessing both NMN adenylytransferase (NMNAT; EC ) and ribosylnicotinamide kinase (RNK; EC ) activities. Its function is essential for the growth and survival of H. influenzae and thus may present a new highly specific anti-infectious drug target. We have solved the crystal structure of hiNadR complexed with NAD using the selenomethionine MAD phasing method. The structure reveals the presence of two distinct domains. The N-terminal domain that hosts the NMNAT activity is closely related to archaeal NMNAT, whereas the C-terminal domain, which has been experimentally demonstrated to possess ribosylnicotinamide kinase activity, is structurally similar to yeast thymidylate kinase and several other P-loop-containing kinases. There appears to be no cross-talk between the two active sites. The bound NAD at the active site of the NMNAT domain reveals several critical interactions between NAD and the protein. There is also a second non-active-site NAD molecule associated with the C-terminal RNK domain that adopts a highly folded conformation with the nicotinamide ring stacking over the adenine base. Whereas the RNK domain of the hiNadR structure presented here is the first structural characterization of a ribosylnicotinamide kinase from any organism, the NMNAT domain of hiNadR defines yet another member of the pyridine nucleotide adenylyltransferase family.

PubMed: 12068016
DOI: 10.1074/jbc.M204368200

Experimental method

X-RAY DIFFRACTION (2.9 Å)