Crystal structure of the human vascular adhesion protein-1: unique structural features with functional implications.
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.
Airenne
Tomi T
TT
Department of Biochemistry and Pharmacy, Abo Akademi University, FIN-20520 Turku, Finland.
Nymalm
Yvonne
Y
Kidron
Heidi
H
Smith
David J
DJ
Pihlavisto
Marjo
M
Salmi
Marko
M
Jalkanen
Sirpa
S
Johnson
Mark S
MS
Salminen
Tiina A
TA
D006631:Amine Oxidase (Copper-Containing) / Q000737:chemistry* / Q000378:metabolism; D000595:Amino Acid Sequence; D001665:Binding Sites; D015815:Cell Adhesion Molecules / Q000737:chemistry* / Q000378:metabolism; D018360:Crystallography, X-Ray; D019281:Dimerization; D006031:Glycosylation; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D017434:Protein Structure, Tertiary
D015815:Cell Adhesion Molecules; C076668:AOC3 protein, human; D006631:Amine Oxidase (Copper-Containing)