PDBsum entry: 1aec

Hydrolase

PDB id: 1aec

Contents

Protein chain

218 a.a. *

Ligands

E64

Waters ×268

* Residue conservation analysis

PDB id:

1aec

Name:

Hydrolase

Title:

Crystal structure of actinidin-e-64 complex+

Structure:

Actinidin. Chain: a. Engineered: yes

Source:

Actinidia chinensis. Organism_taxid: 3625

Resolution:

1.86Å R-factor: 0.145

Authors:

K.I.Varughese

Key ref:

K.I.Varughese et al. (1992). Crystal structure of an actinidin-E-64 complex. Biochemistry, 31, 5172-5176. PubMed id: 1606141 DOI: 10.1021/bi00137a012

Date:

05-Feb-92 Release date: 31-Oct-93

Protein chain

P00785  (ACTN_ACTCH) -  Actinidain

Seq: 380 a.a.

Struc: 218 a.a.*

* PDB and UniProt seqs differ at 1 residue position (black cross)

Enzyme reactions

• Enzyme class: E.C.3.4.22.14 - Actinidain.
• Reaction: Specificity close to that of papain.

 Gene Ontology (GO) functional annotation 

• Biological process: proteolysis (1 term)
• Biochemical function: cysteine-type peptidase activity (2 terms)

DOI no: 10.1021/bi00137a012

Biochemistry 31:5172-5176 (1992)

PubMed id: 1606141

Crystal structure of an actinidin-E-64 complex.

K.I.Varughese, Y.Su, D.Cromwell, S.Hasnain, N.H.Xuong.

ABSTRACT

E-64, 1-(L-trans-epoxysuccinylleucylamino)-4-guanidinobutane, is a potent and highly selective irreversible inhibitor of cysteine proteases. The crystal structure of a complex of actinidin and E-64 has been determined at 1.86-A resolution by using the difference Fourier method and refined to an R-factor of 14.5%. The electron density map clearly shows that the C2 atom of the E-64 epoxide ring is covalently bonded to the S atom of the active-site cysteine 25. The charged carboxyl group of E-64 forms four H-bonds with the protein and thus may play an important role in favorably positioning the inhibitor molecule for nucleophilic attack by the active-site thiolate anion. The interaction features between E-64 and actinidin are very similar to those seen in the papain-E-64 complex; however, the amino-4-guanidinobutane group orients differently. The crystals of the actinidin-E-64 complex diffracted much better than the papain-E-64 complex, and consequently the present study provides more precise geometrical information on the binding of the inhibitor. Moreover, this study provides yet another confirmation that the binding of E-64 is at the S subsites and not at the S' subsites as has been previously proposed. The original actinidin structure has been revised using the new cDNA sequence information.