1GVX

Endothiapepsin complexed with H256

Summary for 1GVX

• Entry DOI: 10.2210/pdb1gvx/pdb
• Related: 1E5O 1E80 1E81 1E82 1EED 1ENT 1EPL 1EPM 1EPN 1EPO 1EPP 1EPQ 1EPR 1ER8 1GKT 1GVT 1GVU 1GVV 1GVW 2ER0 2ER6 2ER7 2ER9 3ER3 3ER5 4APE 4ER1 4ER2 4ER4 5ER1 5ER2
• Related PRD ID: PRD_000346
• Descriptor: ENDOTHIAPEPSIN, INHIBITOR H256, SULFATE ION, ... (4 entities in total)
• Functional Keywords: hydrolase, aspartic proteinase mechanism, tetrahedral intermediate, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• Biological source: ENDOTHIA PARASITICA (CHESTNUT BLIGHT FUNGUS); More
• Total number of polymer chains: 2
• Total formula weight: 34899.98

Authors

Coates, L.,Erskine, P.T.,Crump, M.P.,Wood, S.P.,Cooper, J.B. (deposition date: 2002-02-27, release date: 2002-07-04, Last modification date: 2023-12-13)

Primary citation

Coates, L.,Erskine, P.T.,Crump, M.P.,Wood, S.P.,Cooper, J.B.
Five Atomic Resolution Structures of Endothiapepsin Inhibitor Complexes: Implications for the Aspartic Proteinase Mechanism
J.Mol.Biol., 318:1405-, 2002

PubMed Abstract: Endothiapepsin is derived from the fungus Endothia parasitica and is a member of the aspartic proteinase class of enzymes. This class of enzyme is comprised of two structurally similar lobes, each lobe contributing an aspartic acid residue to form a catalytic dyad that acts to cleave the substrate peptide bond. The three-dimensional structures of endothiapepsin bound to five transition state analogue inhibitors (H189, H256, CP-80,794, PD-129,541 and PD-130,328) have been solved at atomic resolution allowing full anisotropic modelling of each complex. The active sites of the five structures have been studied with a view to studying the catalytic mechanism of the aspartic proteinases by locating the active site protons by carboxyl bond length differences and electron density analysis. In the CP-80,794 structure there is excellent electron density for the hydrogen on the inhibitory statine hydroxyl group which forms a hydrogen bond with the inner oxygen of Asp32. The location of this proton has implications for the catalytic mechanism of the aspartic proteinases as it is consistent with the proposed mechanism in which Asp32 is the negatively charged aspartate. A number of short hydrogen bonds (approximately 2.6 A) with ESD values of around 0.01 A that may have a role in catalysis have been identified within the active site of each structure; the lengths of these bonds have been confirmed using NMR techniques. The possibility and implications of low barrier hydrogen bonds in the active site are considered.

PubMed: 12083527
DOI: 10.1016/S0022-2836(02)00197-3

Experimental method

X-RAY DIFFRACTION (1 Å)