2c11

From Proteopedia

Revision as of 15:49, 5 November 2007

CRYSTAL STRUCTURE OF THE 2-HYDRAZINOPYRIDINE OF SEMICARBAZIDE-SENSITIVE AMINE OXIDASE

Overview

Semicarbazide-sensitive amine oxidase (SSAO) belongs to a ubiquitous, family of copper-containing amine oxidases (CuAOs). SSAO is also known as, vascular adhesion protein-1 (VAP-1) and has been identified as one of the, adhesion molecules involved in the leukocyte-extravasation process. The, structure of a truncated soluble form of human SSAO has been solved and, refined to 2.5 A. As expected, SSAO is a homodimer with a fold typical of, the CuAO family. The topaquinone (TPQ) cofactor and a copper ion, characteristic of CuAOs are present in the active site, with the TPQ in, the active ;off-copper' conformation. The structure reveals that a leucine, residue (Leu469) located adjacent to the active site could function as a, gate controlling its accessibility. An RGD motif is displayed on the, surface, where it could be involved in integrin binding and possibly play, a role in the shedding of SSAO from the membrane. Carbohydrate moieties, are observed at five of six potential N-glycosylation sites. Carbohydrates, attached to Asn232 flank the active-site entrance and might influence, substrate specificity. The structure of an adduct of SSAO and the, irreversible inhibitor 2-hydrazinopyridine has been solved and refined to, 2.9 A resolution. Together, these structures will aid efforts to identify, natural substrates, provide valuable information for the design of, specific inhibitors and direct further studies.

About this Structure

2C11 is a Single protein structure of sequence from Homo sapiens with NAG, NDG, CA, CU, CL and PAQ as ligands. Active as Amine oxidase (copper-containing), with EC number 1.4.3.6 Structure known Active Site: AC1. Full crystallographic information is available from OCA.

Reference

Structure of human semicarbazide-sensitive amine oxidase/vascular adhesion protein-1., Jakobsson E, Nilsson J, Ogg D, Kleywegt GJ, Acta Crystallogr D Biol Crystallogr. 2005 Nov;61(Pt 11):1550-62. Epub 2005, Oct 19. PMID:16239734

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