PDBsum entry 2vs2

Hydrolase/hydrolase inhibitor

PDB id: 2vs2

Contents

Protein chain

329 a.a.

Ligands

0QS

DOD ×220

References listed in PDB file

Key reference

• Title: The catalytic mechanism of an aspartic proteinase explored with neutron and x-Ray diffraction.
• Authors: L.Coates, H.F.Tuan, S.Tomanicek, A.Kovalevsky, M.Mustyakimov, P.Erskine, J.Cooper.
• Ref.: J Am Chem Soc, 2008, 130, 7235-7237.
• PubMed id: 18479128

Abstract

Hydrogen atoms play key roles in enzyme mechanism, but as this study shows, even high-quality X-ray data to a resolution of 1 A cannot directly visualize them. Neutron diffraction, however, can locate deuterium atoms even at resolutions around 2 A. Both neutron and X-ray diffraction data have been used to investigate the transition state of the aspartic proteinase endothiapepsin. The different techniques reveal a different part of the story, revealing the clearest picture yet of the catalytic mechanism by which the enzyme operates. Room temperature neutron and X-ray diffraction data were used in a newly developed joint refinement software package to visualize deuterium atoms within the active site of the enzyme when a gem-diol transition state analogue inhibitor is bound at the active site. These data were also used to estimate their individual occupancy, while analysis of the differences between the bond lengths of the catalytic aspartates was performed using atomic resolution X-ray data. The two methods are in agreement on the protonation state of the active site with a transition state analogue inhibitor bound confirming the catalytic mechanism at which the enzyme operates.

Secondary reference #1

• Title: Preliminary neutron and ultrahigh-Resolution X-Ray diffraction studies of the aspartic proteinase endothiapepsin cocrystallized with a gem-Diol inhibitor.
• Authors: H.F.Tuan, P.Erskine, P.Langan, J.Cooper, L.Coates.
• Ref.: Acta Crystallogr Sect F Struct Biol Cryst Commun, 2007, 63, 1080-1083.
• PubMed id: 18084100