2JJJ

Endothiapepsin in complex with a gem-diol inhibitor.

Summary for 2JJJ

• Entry DOI: 10.2210/pdb2jjj/pdb
• Related: 1E5O 1E80 1E81 1E82 1EED 1ENT 1EPL 1EPM 1EPN 1EPO 1EPP 1EPQ 1EPR 1ER8 1GKT 1GVT 1GVU 1GVV 1GVW 1GVX 1OD1 1OEW 1OEX 2ER0 2ER6 2ER7 2ER9 2JJI 2V00 2VS2 3ER3 3ER5 4APE 4ER1 4ER2 4ER4 5ER1 5ER2
• Related PRD ID: PRD_000361
• Descriptor: ENDOTHIAPEPSIN, N~2~-[(2R)-2-benzyl-3-(tert-butylsulfonyl)propanoyl]-N-{(1R)-1-(cyclohexylmethyl)-3,3-difluoro-2,2-dihydroxy-4-[(2-morpholin-4-ylethyl)amino]-4-oxobutyl}-3-(1H-imidazol-3-ium-4-yl)-L-alaninamide, SULFATE ION, ... (4 entities in total)
• Functional Keywords: acid proteinase, aspartyl protease, zymogen, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• Biological source: CRYPHONECTRIA PARASITICA (CHESNUT BLIGHT FUNGUS)
• Total number of polymer chains: 1
• Total formula weight: 34965.03

Authors

Coates, L.,Tuan, H.-F.,Tomanicek, S.J.,Kovalevsky, A.,Mustyakimov, M.,Erskine, P.,Cooper, J. (deposition date: 2008-04-09, release date: 2008-05-27, Last modification date: 2023-11-15)

Primary citation

Coates, L.,Tuan, H.-F.,Tomanicek, S.J.,Kovalevsky, A.,Mustyakimov, M.,Erskine, P.,Cooper, J.
The Catalytic Mechanism of an Aspartic Proteinase Explored with Neutron and X-Ray Diffraction
J.Am.Chem.Soc., 130:7235-, 2008

PubMed 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.

PubMed: 18479128
DOI: 10.1021/JA801269X

Experimental method

X-RAY DIFFRACTION (1 Å)