PDBsum entry 1sp4

Hydrolase/hydrolase inhibitor

PDB id: 1sp4

Contents

Protein chains

48 a.a. *

205 a.a. *

Ligands

EP2

Waters ×176

* Residue conservation analysis

PDB id:

1sp4

Name:

Hydrolase/hydrolase inhibitor

Title:

Crystal structure of ns-134 in complex with bovine cathepsin b: a two headed epoxysuccinyl inhibitor extends along the whole active site cleft

Structure:

Cathepsin b. Chain: a. Fragment: light chain. Cathepsin b. Chain: b. Fragment: heavy chain. Ec: 3.4.22.1

Source:

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

Biol. unit:

Trimer (from PQS)

Resolution:

2.20Å R-factor: 0.194

Authors:

I.Stern,N.Schaschke,L.Moroder,D.Turk

Key ref:

I.Stern et al. (2004). Crystal structure of NS-134 in complex with bovine cathepsin B: a two-headed epoxysuccinyl inhibitor extends along the entire active-site cleft. Biochem J, 381, 511-517. PubMed id: 15084146

Date:

16-Mar-04 Release date: 04-May-04

Protein chain

P07688  (CATB_BOVIN) -  Cathepsin B from Bos taurus

Seq: 335 a.a.

Struc: 48 a.a.

Protein chain

P07688  (CATB_BOVIN) -  Cathepsin B from Bos taurus

Seq: 335 a.a.

Struc: 205 a.a.*

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

Enzyme reactions

• Enzyme class: Chains A, B: 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.

Biochem J 381:511-517 (2004)

PubMed id: 15084146

Crystal structure of NS-134 in complex with bovine cathepsin B: a two-headed epoxysuccinyl inhibitor extends along the entire active-site cleft.

I.Stern, N.Schaschke, L.Moroder, D.Turk.

ABSTRACT

The crystal structure of the inhibitor NS-134 in complex with bovine cathepsin B reveals that functional groups attached to both sides of the epoxysuccinyl reactive group bind to the part of active-site cleft as predicted. The -Leu-Pro-OH side binds to the primed binding sites interacting with the His110 and His111 residues with its C-terminal carboxy group, whereas the -Leu-Gly-Meu (-Leu-Gly-Gly-OMe) part (Meu, methoxycarbonylmethyl) binds along the non-primed binding sites. Comparison with the propeptide structures of cathepsins revealed that the binding of the latter part is least similar to the procathepsin B structure; this result, together with the two-residue shift in positioning of the Leu-Gly-Gly part, suggests that the propeptide structures of the cognate enzymes may not be the best starting point for the design of reverse binding inhibitors.