RSS

PDB:2GVG

Protein Name

Nicotinamide phosphoribosyltransferase (NMPRTase)

Species

Human

Biological Context

Nicotinamide phosphoribosyltransferase (NMPRTase) has important roles of biological processes in nucleotide metabolism. It replenishes the NAD level by biosynthesis, salvaging the breakdown product nicotinamide (NM) and converting it to nicotinamide mononucleotide (NMN). NMPRTase expression is upregulated in cancers, which makes this enzyme an attractive target for developement of new anticancer agents. NMPRTase was originally identified as a secreted growth factor for early B cells and was named pre-B-cell colony-enhancing factor (PBEF). After that, it was found that visceral fat cell produced NMPRTase and so this enzyme was called 'visfatin'. At the same time, it was suggested that NMPRTase has insulin-mimeric effects. So this enzyme is expected to have the potential to contribute antidiabetes therapies.

Structure Description

2gvg2gvg_x2gvg_y

Here shows the structure of NMPRTase. Although the pictures above have six monomers, this enzyme has activity when it forms dimer. This atomic models contain residues 9-41 and 54-484 of NMPRTase in this picture. In monomer, this enzyme contains 22 β-strands and 15 α-helices and can be divided into three domains, A, B and C (colored orange, cyan, and yellow, respectively, in Fig 1). As a dimer (Fig 2), the two monomers are arranged head to tail, with domain A in one monomer contacting domain B in the other. The domain C is far from the interface, so this domain seems not to have the role of staiblizng the dimer. The reaction product, NMN, is bound near the top of the central β-sheet in domain B. The active site is located in the dimer interface. These suggest NMPRTase can be active only in its dimeric form.

Below shows the pictures from some other angles. The monomer is colored according as domain as mentioned above (Fig 1). The pink helix conects domain A and B. NMN is shown by stick model. The dimeric form of NMPRTase is shown in Fig 2. The binding mode of NMN and the active site of this enzyme are shown in Fig 3.

closeup closeup closeup
Fig 1: Monomer Fig 2: Dimer Fig 3: Binding mode of NMN

Protein Data Bank (PDB)

References

Source

Khan, J.A. Tao, X. Tong, L.; "Molecular basis for the inhibition of human NMPRTase, a novel target for anticancer agents."; Nat.Struct.Mol.Biol.; (2006) 13:582-588 PubMed:16783377.

Others

author: Daisuke Kuroda


Japanese version:PDB:2GVG