PDBsum entry: 1eed

Hydrolase/hydrolase inhibitor

PDB id: 1eed

Contents

Protein chain

330 a.a. *

Ligands

0EO

Waters ×278

* Residue conservation analysis

PDB id:

1eed

Name:

Hydrolase/hydrolase inhibitor

Title:

X-ray crystallographic analysis of inhibition of endothiapep cyclohexyl renin inhibitors

Structure:

Endothiapepsin. Chain: p. Engineered: yes

Source:

Cryphonectria parasitica. Chestnut blight fungus. Organism_taxid: 5116

Biol. unit:

Dimer (from PQS)

Resolution:

2.00Å R-factor: 0.152

Authors:

T.L.Blundell,C.Frazao,J.B.Cooper

Key ref:

J.Cooper et al. (1992). X-ray crystallographic analysis of inhibition of endothiapepsin by cyclohexyl renin inhibitors. Biochemistry, 31, 8142-8150. PubMed id: 1525155 DOI: 10.1021/bi00150a005

Date:

15-Jun-92 Release date: 31-Jan-94

Protein chain

P11838  (CARP_CRYPA) -  Endothiapepsin

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.

 Gene Ontology (GO) functional annotation 

• Biological process: proteolysis (1 term)
• Biochemical function: aspartic-type endopeptidase activity (1 term)

DOI no: 10.1021/bi00150a005

Biochemistry 31:8142-8150 (1992)

PubMed id: 1525155

X-ray crystallographic analysis of inhibition of endothiapepsin by cyclohexyl renin inhibitors.

J.Cooper, W.Quail, C.Frazao, S.I.Foundling, T.L.Blundell, C.Humblet, E.A.Lunney, W.T.Lowther, B.M.Dunn.

ABSTRACT

The crystal structures of endothiapepsin, a fungal aspartic proteinase (EC 3.4.23.6), cocrystallized with two oligopeptide renin inhibitors, PD125967 and PD125754, have been determined at 2.0-A resolution and refined to R-factors of 0.143 and 0.153, respectively. These inhibitors, which are of the hydroxyethylene and statine types, respectively, possess a cyclohexylalanine side chain at P1 and have interesting functionalities at the P3 position which, until now, have not been subjected to crystallographic analysis. PD125967 has a bis(1-naphthylmethyl)acetyl residue at P3, and PD125754 possesses a hydroxyethylene analogue of the P3-P2 peptide bond for proteolytic stability. The structures reveal that the S3 pocket accommodates one naphthyl ring with conformational changes of the Asp 77 and Asp 114 side chains, the other naphthyl group residing in the S4 region. The P3-P2 hydroxyethylene analogue of PD125754 forms a hydrogen bond with the NH of Thr 219, thereby making the same interaction with the enzyme as the equivalent peptide groups of all inhibitors studied so far. The absence of side chains at the P2 and P1' positions of this inhibitor allows water molecules to occupy the respective pockets in the complex. The relative potencies of PD125967 and PD125754 for endothiapepsin are consistent with the changes in solvent-accessible area which take place on inhibitor binding.