1ISF

Crystal Structure Analysis of BST-1/CD157

Summary for 1ISF

• Entry DOI: 10.2210/pdb1isf/pdb
• Related: 1ISG 1ISH 1ISI 1ISJ 1ISM
• Descriptor: bone marrow stromal cell antigen 1, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, GLYCEROL, ... (4 entities in total)
• Functional Keywords: adp-ribosylcyclase, nad glycohydrolase, cns, hydrolase
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 2
• Total formula weight: 61469.45

Authors

Yamamoto-Katayama, S.,Ariyoshi, M.,Ishihara, K.,Hirano, T.,Jingami, H.,Morikawa, K. (deposition date: 2001-12-05, release date: 2002-03-13, Last modification date: 2024-11-13)

Primary citation

Yamamoto-Katayama, S.,Ariyoshi, M.,Ishihara, K.,Hirano, T.,Jingami, H.,Morikawa, K.
Crystallographic studies on human BST-1/CD157 with ADP-ribosyl cyclase and NAD glycohydrolase activities.
J.Mol.Biol., 316:711-723, 2002

PubMed Abstract: cADPR is the novel second messenger that elicits calcium release from intracellular calcium stores and works independently of IP(3). In mammals, the ADP-ribosyl cyclase function is found in two membrane proteins, CD38 and BST-1/CD157. These enzymes, exposed extracellularly, bear cADPR hydrolase and NAD glycohydrolase activities. In spite of its functional importance, the structural basis of these enzymatic reactions remains elusive. We determined the crystal structures of the extracellular region of human BST-1 at atomic resolution in the free form and in complexes with five substrate analogues: nicotinamide, NMN, ATPgammaS, ethenoNADP, and ethenoNAD. The three-dimensional structural views of the reaction centre with these ligands revealed the mode of substrate binding and the catalytic mechanism of the multifunctional enzymatic reactions. In each catalytic cleft of the dimeric enzyme, substrates are recognized predominantly through van der Waals interactions with two tryptophan residues, and thereby the N-glycosidic bond of NAD is correctly exposed near a catalytic glutamate residue. Its carboxyl side-chain stabilizes the catalytic intermediate of the S(N)-1 type reaction. This conformation of the catalytic cleft also implies the mechanism of cyclization between the adenine base and the ribose. The three key residues are invariant among the sequences of BST-1, CD38, and Aplysia cyclase, and hence this substrate recognition mode and catalytic scheme appear to be common in the cyclase family.

PubMed: 11866528
DOI: 10.1006/jmbi.2001.5386

Experimental method

X-RAY DIFFRACTION (2.5 Å)