PDBsum entry 1epp

Hydrolase/hydrolase inhibitor

PDB id: 1epp

Contents

Protein chain

330 a.a. *

Ligands

SO4 ×2

1Z1

Waters ×260

* Residue conservation analysis

PDB id:

1epp

Name:

Hydrolase/hydrolase inhibitor

Title:

Endothia aspartic proteinase (endothiapepsin) complexed with pd-130, 693 (mas phe lys+mtf sta mba)

Structure:

Endothiapepsin. Chain: e. Engineered: yes

Source:

Cryphonectria parasitica. Chestnut blight fungus. Organism_taxid: 5116

Biol. unit:

Dimer (from PQS)

Resolution:

1.90Å R-factor: 0.160

Authors:

B.A.Wallace,J.B.Cooper,T.L.Blundell

Key ref:

E.A.Lunney et al. (1993). Analyses of ligand binding in five endothiapepsin crystal complexes and their use in the design and evaluation of novel renin inhibitors. J Med Chem, 36, 3809-3820. PubMed id: 8254610 DOI: 10.1021/jm00076a008

Date:

27-Jul-94 Release date: 20-Dec-94

Protein chain

P11838  (CARP_CRYPA) -  Endothiapepsin from Cryphonectria parasitica

Seq: 419 a.a.

Struc: 330 a.a.

Enzyme reactions

• Enzyme class: E.C.3.4.23.22 - endothiapepsin.
• Reaction: Hydrolysis of proteins with broad specificity similar to that of pepsin A, preferring hydrophobic residues at P1 and P1', but does not cleave 14-Ala-|-Leu-15 in the B chain of insulin or Z-Glu-Tyr. Clots milk.

DOI no: 10.1021/jm00076a008

J Med Chem 36:3809-3820 (1993)

PubMed id: 8254610

Analyses of ligand binding in five endothiapepsin crystal complexes and their use in the design and evaluation of novel renin inhibitors.

E.A.Lunney, H.W.Hamilton, J.C.Hodges, J.S.Kaltenbronn, J.T.Repine, M.Badasso, J.B.Cooper, C.Dealwis, B.A.Wallace, W.T.Lowther.

ABSTRACT

Five renin inhibitors were cocrystallized with endothiapepsin, a fungal enzyme homologous to renin. Crystal structures of inhibitor-bound complexes have provided invaluable insight regarding the three-dimensional structure of the aspartic proteinase family of enzymes, as well as the steric and polar interactions that occur between the proteins and the bound ligands. Beyond this, subtleties of binding have been revealed, including multiple subsite binding modes and subsite interdependencies. This information has been applied in the design of novel potent renin inhibitors and in the understanding of structure-activity relationships and enzyme selectivities.