PDBsum entry 1mcv

Hydrolase

PDB id: 1mcv

Contents

Protein chains

240 a.a. *

28 a.a. *

Ligands

SO4

Metals

_CA

Waters ×353

* Residue conservation analysis

PDB id:

1mcv

Name:

Hydrolase

Title:

Crystal structure analysis of a hybrid squash inhibitor in complex with porcine pancreatic elastase

Structure:

Elastase 1. Chain: a. Hei-toe i. Chain: i. Synonym: hybrid squash inhibitor hei-toe 1. Engineered: yes

Source:

Sus scrofa. Pig. Organism_taxid: 9823. Synthetic: yes. Other_details: the peptide was chemically synthesized using solid phase peptide synthesis. It was constructed using the trypsin binding loop of squash inhibitor eeti ii, substituted by the sequence of a peptide that was derived from the third domain of the turkey ovomucoid inhibitor.

Biol. unit:

Dimer (from PQS)

Resolution:

1.80Å R-factor: 0.182 R-free: 0.221

Authors:

J.Ay,K.Hilpert,N.Krauss,J.Schneider-Mergener,W.Hoehne

Key ref:

J.Aÿ et al. (2003). Structure of a hybrid squash inhibitor in complex with porcine pancreatic elastase at 1.8 A resolution. Acta Crystallogr D Biol Crystallogr, 59, 247-254. PubMed id: 12554935 DOI: 10.1107/S0907444902020887

Date:

06-Aug-02 Release date: 04-Feb-03

Protein chain

P00772  (CELA1_PIG) -  Chymotrypsin-like elastase family member 1 from Sus scrofa

Seq: 266 a.a.

Struc: 240 a.a.

Protein chain

No UniProt id for this chain

Struc: 28 a.a.

Enzyme reactions

• Enzyme class: Chain A: E.C.3.4.21.36 - pancreatic elastase.
• Reaction: Hydrolysis of proteins, including elastin. Preferential cleavage: Ala-|-Xaa.

DOI no: 10.1107/S0907444902020887

Acta Crystallogr D Biol Crystallogr 59:247-254 (2003)

PubMed id: 12554935

Structure of a hybrid squash inhibitor in complex with porcine pancreatic elastase at 1.8 A resolution.

J.Aÿ, K.Hilpert, N.Krauss, J.Schneider-Mergener, W.Höhne.

ABSTRACT

The crystal structure of porcine pancreatic elastase in complex with a hybrid squash inhibitor (HEI-TOE I; 28 amino acids) has been determined to a resolution of 1.8 A. To construct the hybrid inhibitor, the trypsin-binding loop of the squash inhibitor from Ecballium elaterium was substituted by the sequence of a peptide that was derived from the third domain of the turkey ovomucoid inhibitor and was optimized to inhibit porcine pancreatic elastase. This modification of the squash inhibitor changed its specificity for trypsin to a specificity for porcine pancreatic elastase. Specific interactions of this hybrid inhibitor with porcine pancreatic elastase and the differences from the interactions of the ovomucoid inhibitor with human leukocyte elastase are discussed. The binding loop of the inhibitor adopts a 'canonical' conformation and the scissile bond Leu-Glu remains intact.

Selected figure(s)

Figure 1.
Figure 1 Comparison of the sequence of the inhibitory proteins and the peptide used in this study (P1 position underlined).

Figure 6.
Figure 6 Stereoview of (a) the superposition of the complexes PPE-HEI-TOE I (green/red) and HLE-OMTKY3 (blue/yellow), schematic representation, (b) the hybrid inhibitor HEI-TOE I (red) bound to PPE (green; active-site Ser195 in dark green), important side-chain contacts for the binding-loop sequence PCTLEYMR, (c) the OMTKY3 inhibitor (yellow) bound to human leukocyte elastase (blue; active site Ser195 dark blue), important side-chain contacts for the binding-loop sequence ACTLEYRP.

The above figures are reprinted by permission from the IUCr: Acta Crystallogr D Biol Crystallogr (2003, 59, 247-254) copyright 2003.

Figures were selected by an automated process.