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

Tomi Airenne, Yvonne Nymalm, H Kidron, DJ Smith, M Pihlavisto, M Salmi, S Jalkanen, Mark S Johnson, Tiina Salminen

Tutkimustuotos: LehtiartikkeliArtikkeliTieteellinenvertaisarvioitu

79 Sitaatiot (Scopus)

Abstrakti

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.
AlkuperäiskieliEi tiedossa
Sivut1964–1974
Sivumäärä11
JulkaisuProtein Science
Vuosikerta14
Numero8
DOI - pysyväislinkit
TilaJulkaistu - 2005
OKM-julkaisutyyppiA1 Julkaistu artikkeli, soviteltu

Keywords

  • hVAP-1
  • amine oxidase

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