PDBsum entry 1wnh

Hydrolase inhibitor

PDB id: 1wnh

Contents

Protein chain

220 a.a. *

Waters ×186

* Residue conservation analysis

PDB id:

1wnh

Name:

Hydrolase inhibitor

Title:

Crystal structure of mouse latexin (tissue carboxypeptidase inhibitor)

Structure:

Latexin. Chain: a. Synonym: carboxypeptidase inhibitor. Engineered: yes

Source:

Mus musculus. House mouse. Organism_taxid: 10090. Gene: lxn. Expressed in: escherichia coli. Expression_system_taxid: 562.

Biol. unit:

Dimer (from PQS)

Resolution:

1.83Å R-factor: 0.211 R-free: 0.237

Authors:

A.Aagaard,P.Listwan,N.Cowieson,T.Huber,T.Ravasi,C.A.Wells, J.U.Flanagan,D.A.Hume,B.Kobe,J.L.Martin

Key ref:

A.Aagaard et al. (2005). An inflammatory role for the mammalian carboxypeptidase inhibitor latexin: relationship to cystatins and the tumor suppressor TIG1. Structure, 13, 309-317. PubMed id: 15698574 DOI: 10.1016/j.str.2004.12.013

Date:

04-Aug-04 Release date: 15-Feb-05

Protein chain

P70202  (LXN_MOUSE) -  Latexin from Mus musculus

Seq: 222 a.a.

Struc: 220 a.a.

DOI no: 10.1016/j.str.2004.12.013

Structure 13:309-317 (2005)

PubMed id: 15698574

An inflammatory role for the mammalian carboxypeptidase inhibitor latexin: relationship to cystatins and the tumor suppressor TIG1.

A.Aagaard, P.Listwan, N.Cowieson, T.Huber, T.Ravasi, C.A.Wells, J.U.Flanagan, S.Kellie, D.A.Hume, B.Kobe, J.L.Martin.

ABSTRACT

Latexin, the only known mammalian carboxypeptidase inhibitor, has no detectable sequence similarity with plant and parasite inhibitors, but it is related to a human putative tumor suppressor protein, TIG1. Latexin is expressed in the developing brain, and we find that it plays a role in inflammation, as it is expressed at high levels and is inducible in macrophages in concert with other protease inhibitors and potential protease targets. The crystal structure of mouse latexin, solved at 1.83 A resolution, shows no structural relationship with other carboxypeptidase inhibitors. Furthermore, despite a lack of detectable sequence duplication, the structure incorporates two topologically analogous domains related by pseudo two-fold symmetry. Surprisingly, these domains share a cystatin fold architecture found in proteins that inhibit cysteine proteases, suggesting an evolutionary and possibly functional relationship. The structure of the tumor suppressor protein TIG1 was modeled, revealing its putative membrane binding surface.

Selected figure(s)

Figure 4.
Figure 4. Diversity and Similarity in CP Inhibitors, Cystatin, and Monellin
(A-F) Structures of CP inhibitors from (A) potato (4CPA [Rees and Lipscomb, 1982]) and (B) leech (1DTV [Reverter et al., 2000]) are very different from the structure of mammalian CP inhibitor, (C) latexin. However, latexin (N-terminal domain, [D]) is structurally related to proteins in the (E) cystatin (cysteine protease inhibitor, chicken cystatin) (1CEW [Bode et al., 1988]) and (F) monellin (sweet-tasting protein) (1MOL [Somoza et al., 1993]) fold family.

The above figure is reprinted by permission from Cell Press: Structure (2005, 13, 309-317) copyright 2005.

Figure was selected by the author.