4OGW

Structure of a human CD38 mutant complexed with NMN

4OGW の概要

• エントリーDOI: 10.2210/pdb4ogw/pdb
• 分子名称: ADP-ribosyl cyclase 1, BETA-NICOTINAMIDE RIBOSE MONOPHOSPHATE (3 entities in total)
• 機能のキーワード: adp-ribosyl cyclase, hydrolase
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Membrane; Single-pass type II membrane protein: P28907
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 29997.84

構造登録者

Shewchuk, L.M.,Preugschat, F.,Carter, L.H.,Boros, E.E.,Moyer, M.B.,Stewart, E.L.,Porter, D.J.T. (登録日: 2014-01-16, 公開日: 2014-10-08, 最終更新日: 2024-11-20)

主引用文献

Preugschat, F.,Carter, L.H.,Boros, E.E.,Porter, D.J.,Stewart, E.L.,Shewchuk, L.M.
A pre-steady state and steady state kinetic analysis of the N-ribosyl hydrolase activity of hCD157.
Arch.Biochem.Biophys., 564C:156-163, 2014

PubMed Abstract: hCD157 catalyzes the hydrolysis of nicotinamide riboside (NR) and nicotinic acid riboside (NAR). The release of nicotinamide or nicotinic acid from NR or NAR was confirmed by spectrophotometric, HPLC and NMR analyses. hCD157 is inactivated by a mechanism-based inhibitor, 2'-deoxy-2'-fluoro-nicotinamide arabinoside (fNR). Modification of the enzyme during the catalytic cycle by NR, NAR, or fNR increased the intrinsic protein fluorescence by approximately 50%. Pre-steady state and steady state data were used to derive a minimal kinetic scheme for the hydrolysis of NR. After initial complex formation a reversible step (360 and 30s(-1)) is followed by a slow irreversible step (0.1s(-1)) that defined the rate limiting step, or kcat. The calculated KMapp value for NR in the hydrolytic reaction is 6nM. The values of the kinetic constants suggest that one biological function of cell-surface hCD157 is to bind and slowly hydrolyze NR, possibly converting it to a ligand-activated receptor. Differences in substrate preference between hCD157 and hCD38 were rationalized through a comparison of the crystal structures of the two proteins. This comparison identified several residues in hCD157 (F108 and F173) that can potentially hinder the binding of dinucleotide substrates (NAD+).

PubMed: 25250980
DOI: 10.1016/j.abb.2014.09.008

実験手法

X-RAY DIFFRACTION (2.05 Å)