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.
Alkuperäiskieli | Ei tiedossa |
---|---|
Sivut | 1964–1974 |
Sivumäärä | 11 |
Julkaisu | Protein Science |
Vuosikerta | 14 |
Numero | 8 |
DOI - pysyväislinkit | |
Tila | Julkaistu - 2005 |
OKM-julkaisutyyppi | A1 Julkaistu artikkeli, soviteltu |
Keywords
- hVAP-1
- amine oxidase