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

References listed in PDB file

Key reference

Title

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

Authors

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

Ref.

Acta Crystallogr D Biol Crystallogr, 2003, 59, 247-254. [DOI no: 10.1107/S0907444902020887]

PubMed id

12554935

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.

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.

Secondary reference #1

Title

Atomic resolution structure of native porcine pancreatic elastase at 1.1 a.

Authors

M.Würtele, M.Hahn, K.Hilpert, W.Höhne.

Ref.

Acta Crystallogr D Biol Crystallogr, 2000, 56, 520-523. [DOI no: 10.1107/S0907444900000299]

PubMed id

10739939

Figure 2.
Figure 2 The catalytic triad of PPE. (a) 2F[o] - F[c] map contoured at 3.5 (blue) shows atomic resolution of active-site residues of the final model (SUL1: sulfate). (b) 2F[o] - F[c] map of anisotropic B-factor model with the HN 1 omitted contoured at 2.5 (blue). F[o] - F[c] map is contoured at 2.5 (red). (c) Thermal ellipsoid representation of active-site residues was made with ORTEX 7e (McArdle, 1995[McArdle, P. (1995). J. Appl. Cryst. 28, 65.]; Burnett & Johnson, 1996[Burnett, M. N. & Johnson, C. K. (1996). ORTEP III: Oak Ridge Thermal Ellipsoid Plot Program for Crystal Structure Illustrations. Report ORNL-6895. Oak Ridge National Laboratory, Tennessee, USA.]). Putative hydrogen bonds are shown as dotted lines.

The above figure is reproduced from the cited reference with permission from the IUCr

Secondary reference #2

Title

X-Ray crystal structure of the complex of human leukocyte elastase (pmn elastase) and the third domain of the turkey ovomucoid inhibitor.

Authors

W.Bode, A.Z.Wei, R.Huber, E.Meyer, J.Travis, S.Neumann.

Ref.

Embo J, 1986, 5, 2453-2458.

PubMed id

3640709

Secondary reference #3

Title

The refined 2.0 a X-Ray crystal structure of the complex formed between bovine beta-Trypsin and cmti-I, A trypsin inhibitor from squash seeds (cucurbita maxima). Topological similarity of the squash seed inhibitors with the carboxypeptidase a inhibitor from potatoes.

Authors

W.Bode, H.J.Greyling, R.Huber, J.Otlewski, T.Wilusz.

Ref.

Febs Lett, 1989, 242, 285-292.

PubMed id

2914611