PDBsum entry: 1ito

Hydrolase

PDB id: 1ito

Contents

Protein chain

251 a.a. *

Ligands

E6C

Waters ×130

* Residue conservation analysis

PDB id:

1ito

Name:

Hydrolase

Title:

Crystal structure analysis of bovine spleen cathepsin b- e64c complex

Structure:

Cathepsin b. Chain: a. Ec: 3.4.22.1

Source:

Bos taurus. Cattle. Organism_taxid: 9913. Tissue: spleen

Biol. unit:

Dimer (from PQS)

Resolution:

2.29Å R-factor: 0.197 R-free: 0.239

Authors:

A.Yamamoto,T.Tomoo,K.Matsugi,T.Hara,Y.In,M.Murata, K.Kitamura,T.Ishida

Key ref:

A.Yamamoto et al. (2002). Structural basis for development of cathepsin B-specific noncovalent-type inhibitor: crystal structure of cathepsin B-E64c complex. Biochim Biophys Acta, 1597, 244-251. PubMed id: 12044902 DOI: 10.1016/S0167-4838(02)00284-4

Date:

19-Jan-02 Release date: 19-Jan-03

Protein chain

P07688  (CATB_BOVIN) -  Cathepsin B

Seq: 335 a.a.

Struc: 251 a.a.

Enzyme reactions

• Enzyme class: E.C.3.4.22.1 - Cathepsin B.
• Reaction: Hydrolysis of proteins with broad specificity for peptide bonds. Preferentially cleaves -Arg-Arg-|-Xaa bonds in small molecule substrates (thus differing from cathepsin L). In addition to being an endopeptidase, shows peptidyl-dipeptidase activity, liberating C-terminal dipeptides.

 Gene Ontology (GO) functional annotation 

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

DOI no: 10.1016/S0167-4838(02)00284-4

Biochim Biophys Acta 1597:244-251 (2002)

PubMed id: 12044902

Structural basis for development of cathepsin B-specific noncovalent-type inhibitor: crystal structure of cathepsin B-E64c complex.

A.Yamamoto, K.Tomoo, K.Matsugi, T.Hara, Y.In, M.Murata, K.Kitamura, T.Ishida.

ABSTRACT

In order to elucidate the substrate specificity of the Sn subsites (n=1-3) of cathepsin B, its crystal structure inhibited by E64c [(+)-(2S,3S)-3-(1-[N-(3-methylbutyl)amino]-leucylcarbonyl)oxirane-2-carboxylic was analyzed by the X-ray diffraction method. Iterative manual rebuilding and convenient conjugate refinement of structure decreased R- and free R-factors to 19.7% and to 23.9%, respectively, where 130 water molecules were included for the refinement using 14,759 independent reflections from 10 to 2.3 A resolution. The epoxy carbonyl carbon of E64c was covalently bonded to the Cys(29) S(gamma) atom and the remaining parts were located at Sn subsites (n=1-3). The substrate specificity of these subsites was characterized based on their interactions with the inhibitor. Base on these structural data, we developed a novel cathepsin B-specific noncovalent-type inhibitor, which may bind to S2'-S3. The molecular design of possessing structural elements of both CA074 and E64c, assisted by energy minimization and molecular dynamics (MD) simulation, may lead to a new lead noncovalent-type inhibitor.