Crystal structure of the human vascular adhesion protein-1: Unique structural features with functional implications

A1 Journal article (refereed)


Internal Authors/Editors


Publication Details

List of Authors: Airenne TT, Nymalm Y, Kidron H, Smith DJ, Pihlavisto M, Salmi M, Jalkanen S, Johnson MS, Salminen TA
Publisher: COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
Publication year: 2005
Journal: Protein Science
Journal acronym: PROTEIN SCI
Volume number: 14
Issue number: 8
Start page: 1964
End page: 1974
Number of pages: 11
ISSN: 0961-8368


Abstract

The expression of human vascular adhesion protein-1 (hVAP-1) is induced at sites of inflammation where extravasation of lymphocytes from blood to the peripheral tissue occurs. We have solved the X-ray structure of hVAP-1, a human copper amine oxidase (CAO), which is distinguished from other CAOs in being membrane-bound. The dimer structure reveals some intriguing features that may have fundamental roles in the adhesive and enzymatic functions of hVAP-1, especially regarding the role of hVAP-1 in inflammation, lymphocyte attachment, and signaling. Firstly, Leu469 at the substrate channel may play a key role in controlling the substrate entry; depending on its conformation, it either blocks or gives access to the active site. Secondly, sugar units are clearly observed at two of the six predicted N-glycosylation sites. Moreover, mutagenesis analysis showed that all of the predicted sites were glycosylated in the protein used for crystallization. Thirdly, the existence of a solvent-exposed RGD motif at the entrance to each active site in hVAP-1 suggests that it may have a functional role.


Keywords

amine oxidase, hVAP-1

Last updated on 2019-20-09 at 08:03