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Structure of human ...
Structure of human semicarbazide-sensitive amine oxidase/vascular adhesion protein-1.
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- Jakobsson, Emma (författare)
- Uppsala universitet,Institutionen för cell- och molekylärbiologi,Strukturell molekylärbiologi
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Nilsson, Joakim (författare)
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Ogg, Derek (författare)
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- Kleywegt, Gerard J (författare)
- Uppsala universitet,Institutionen för cell- och molekylärbiologi,Strukturell molekylärbiologi
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(creator_code:org_t)
- 2005
- 2005
- Engelska.
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Ingår i: Acta Crystallogr D Biol Crystallogr. - 0907-4449. ; 61:Pt 11, s. 1550-62
- Relaterad länk:
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http://www.ncbi.nlm....
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https://urn.kb.se/re...
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Abstract
Ämnesord
Stäng
- 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.
Nyckelord
- Amine Oxidase (Copper-Containing)/antagonists & inhibitors/*chemistry
- Amino Acid Motifs
- Binding Sites
- Cell Adhesion Molecules/antagonists & inhibitors/*chemistry
- Cell Line
- Copper/chemistry
- Crystallography; X-Ray
- Dihydroxyphenylalanine/analogs & derivatives/chemistry
- Humans
- Models; Molecular
- Protein Conformation
- Pyridones/*chemistry/pharmacology
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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