| Autor: |
Singh, S. Kumar, Kurnasov, Oleg V., Chen, Baozhi, Robinson, Howard, Grishin, Nick V., Osterman, Andrei L., Zhang, Hong |
| Zdroj: |
Journal of Biological Chemistry; September 2002, Vol. 277 Issue: 36 p33291-33299, 9p |
| Abstrakt: |
Haemophilus influenzaeNadR protein (hiNadR) has been shown to be a bifunctional enzyme possessing both NMN adenylytransferase (NMNAT; EC 2.7.7.1) and ribosylnicotinamide kinase (RNK; EC 2.7.1.22) activities. Its function is essential for the growth and survival of H. influenzaeand thus may present a new highly specific anti-infectious drug target. We have solved the crystal structure ofhiNadR 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 ofhiNadR defines yet another member of the pyridine nucleotide adenylyltransferase family. |
| Databáze: |
Supplemental Index |
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