PDBsum entry 2cv3

Hydrolase/hydrolase inhibitor

PDB id: 2cv3

Contents

Protein chains

240 a.a. *

11 a.a. *

Waters ×295

* Residue conservation analysis

PDB id:

2cv3

Name:

Hydrolase/hydrolase inhibitor

Title:

Crystal structure of porcine pancreatic elastase complexed with a macroclyclic peptide inhibitor

Structure:

Elastase 1. Chain: a. Inhibitor fr901451. Chain: b

Source:

Sus scrofa. Pig. Organism_taxid: 9823. Flexibacter sp.. Organism_taxid: 1005

Resolution:

1.90Å R-factor: 0.162 R-free: 0.224

Authors:

T.Kinoshita,T.Tada,T.Kitatani

Key ref:

T.Kinoshita et al. (2005). Structure of the complex of porcine pancreatic elastase with a trimacrocyclic peptide inhibitor FR901451. Acta Crystallograph Sect F Struct Biol Cryst Commun, 61, 808-811. PubMed id: 16511165 DOI: 10.1107/S1744309105026047

Date:

31-May-05 Release date: 16-May-06

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: 11 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/S1744309105026047

Acta Crystallograph Sect F Struct Biol Cryst Commun 61:808-811 (2005)

PubMed id: 16511165

Structure of the complex of porcine pancreatic elastase with a trimacrocyclic peptide inhibitor FR901451.

T.Kinoshita, T.Kitatani, M.Warizaya, T.Tada.

ABSTRACT

Porcine pancreatic elastase (PPE) resembles the attractive drug target leukocyte elastase, which has the ability to degrade connective tissue in the body. The crystal structure of PPE complexed with a novel trimacrocyclic peptide inhibitor, FR901451, was solved at 1.9 A resolution. The inhibitor occupied the subsites S3 through S3' of PPE and induced conformational changes in the side chains of Arg64 and Arg226, which are located at the edges of the substrate-binding cleft. Structural comparison of five PPE-inhibitor complexes, including the FR901451 complex and non-ligated PPE, reveals that the residues forming the S2, S1, S1' and S2' subsites in the cleft are rigid, but the two arginine residues playing a part in the S3 and S3' subsites are flexible. Structural comparison of PPE with human leukocyte elastase (HLE) implies that the inhibitor binds to HLE in a similar manner to the FR901451-PPE complex. This structural insight may help in the design of potent elastase inhibitors.

Selected figure(s)

Figure 3.
Figure 3 FR901451 within the 2F[o] - F[c] electron-density map contoured at the 1.0 level. The map around Trp9 is discontinuous and ambiguous.

Figure 4.
Figure 4 Superimposed structures of inhibitors in the crystals. Thr1-Lys4 of FR901451 (magenta sticks) bind to PPE in a similar conformation to the linear inhibitor FR136706 (Kinoshita et al., 2003[Kinoshita, T., Nakanishi, I., Sato, A. & Tada, T. (2003). Bioorg. Med. Chem. Lett. 13, 21-24.]; displayed as blue sticks).

The above figures are reprinted from an Open Access publication published by the IUCr: Acta Crystallograph Sect F Struct Biol Cryst Commun (2005, 61, 808-811) copyright 2005.

Figures were selected by an automated process.