PDBsum entry 1ito

Hydrolase

PDB id

1ito

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Contents

			Protein chain

					251 a.a. *

			Ligands

					E6C

			Waters ×130

* Residue conservation analysis

PDB id:

1ito

Links
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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

PROCHECK

	Headers

	References

Protein chain

P07688 (CATB_BOVIN) - Cathepsin B from Bos taurus

Seq: Struc:					335 a.a. 251 a.a.

Key:

PfamA domain

Secondary structure

CATH domain



		Enzyme reactions

Enzyme class:

E.C.3.4.22.1 - cathepsin B.

[IntEnz] [ExPASy] [KEGG] [BRENDA]

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.

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 acid] 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.

Literature references that cite this PDB file's key reference

PubMed id

Reference

19952439

T.Ishida (2009).
Structural studies of specific intermolecular interactions and self-aggregation of biomolecules and their application to drug design.

Chem Pharm Bull (Tokyo), 57, 1309-1334.

17066390

M.Mladenovic, T.Schirmeister, S.Thiel, W.Thiel, and B.Engels (2007).
The Importance of the Active Site Histidine for the Activity of Epoxide- or Aziridine-Based Inhibitors of Cysteine Proteases.

ChemMedChem, 2, 120-128.

The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time.