2C11

Crystal structure of the 2-hydrazinopyridine of semicarbazide- sensitive amine oxidase

2C11 の概要

• エントリーDOI: 10.2210/pdb2c11/pdb
• 関連するPDBエントリー: 2C10
• 分子名称: MEMBRANE COPPER AMINE OXIDASE, CHLORIDE ION, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (11 entities in total)
• 機能のキーワード: oxidoreductase, adhesion protein-1, 2-hydroxypyridine, metal-binding, cell adhesion, glycoprotein, signal-anchor, tpq, transmembrane
• 由来する生物種: HOMO SAPIENS (HUMAN)
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 336433.26

構造登録者

Jakobsson, E.,Kleywegt, G.J. (登録日: 2005-09-09, 公開日: 2006-09-20, 最終更新日: 2024-10-23)

主引用文献

Jakobsson, E.,Nilsson, J.,Ogg, D.,Kleywegt, G.J.
Structure of human semicarbazide-sensitive amine oxidase/vascular adhesion protein-1.
Acta Crystallogr. D Biol. Crystallogr., 61:1550-1562, 2005

PubMed Abstract: 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.

PubMed: 16239734
DOI: 10.1107/S0907444905028805

実験手法

X-RAY DIFFRACTION (2.9 Å)