PDBsum entry: 1o0e

Hydrolase

PDB id: 1o0e

Contents

Protein chains

208 a.a. *

Ligands

THJ ×2

Waters ×256

* Residue conservation analysis

PDB id:

1o0e

Name:

Hydrolase

Title:

1.9 angstrom crystal structure of a plant cysteine protease c

Structure:

Ervatamin c. Chain: a, b

Source:

Tabernaemontana divaricata. Organism_taxid: 52861

Biol. unit:

Dimer (from PQS)

Resolution:

1.90Å R-factor: 0.177 R-free: 0.190

Authors:

P.G.Thakurta,C.Chakrabarti,S.Biswas,J.K.Dattagupta

Key ref:

P.G.Thakurta et al. (2004). Structural basis of the unusual stability and substrate specificity of ervatamin C, a plant cysteine protease from Ervatamia coronaria. Biochemistry, 43, 1532-1540. PubMed id: 14769029 DOI: 10.1021/bi0357659

Date:

21-Feb-03 Release date: 02-Mar-04

Protein chains

P83654  (ERVC_TABDI) -  Ervatamin-C

Seq: 208 a.a.

Struc: 208 a.a.

 Gene Ontology (GO) functional annotation 

• Cellular component: extracellular region (1 term)
• Biological process: proteolysis (1 term)
• Biochemical function: hydrolase activity (4 terms)

DOI no: 10.1021/bi0357659

Biochemistry 43:1532-1540 (2004)

PubMed id: 14769029

Structural basis of the unusual stability and substrate specificity of ervatamin C, a plant cysteine protease from Ervatamia coronaria.

P.G.Thakurta, S.Biswas, C.Chakrabarti, M.Sundd, M.V.Jagannadham, J.K.Dattagupta.

ABSTRACT

Ervatamin C is an unusually stable cysteine protease from the medicinal plant Ervatamia coronaria belonging to the papain family. Though it cleaves denatured natural proteins with high specific activity, its activity toward some small synthetic substrates is found to be insignificant. The three-dimensional structure and amino acid sequence of the protein have been determined from X-ray diffraction data at 1.9 A (R = 17.7% and R(free) = 19.0%). The overall structure of ervatamin C is similar to those of other homologous cysteine proteases of the family, folding into two distinct left and right domains separated by an active site cleft. However, substitution of a few amino acid residues, which are conserved in the other members of the family, has been observed in both the domains and also at the region of the interdomain cleft. Consequently, the number of intra- and interdomain hydrogen-bonding interactions is enhanced in the structure of ervatamin C. Moreover, a unique disulfide bond has been identified in the right domain of the structure, in addition to the three conserved disulfide bridges present in the papain family. All these factors contribute to an increase in the stability of ervatamin C. In this enzyme, the nature of the S2 subsite, which is the primary determinant of specificity of these proteases, is similar to that of papain, but at the S3 subsite, Ala67 replaces an aromatic residue, and has the effect of eliminating sufficient hydrophobic interactions required for S3-P3 stabilization. This provides the possible explanation for the lower activity of ervatamin C toward the small substrate/inhibitor. This substitution, however, does not affect the binding of denatured natural protein substrates to the enzyme significantly, as there exist a number of additional interactions at the enzyme-substrate interface outside the active site cleft.