The 1.8-A crystal structure of alpha1-acid glycoprotein (Orosomucoid) solved by UV RIP reveals the broad drug-binding activity of this human plasma lipocalin.
J Mol Biol
; 384(2): 393-405, 2008 Dec 12.
Article
de En
| MEDLINE
| ID: mdl-18823996
ABSTRACT
Alpha(1)-acid glycoprotein (AGP) is an important drug-binding protein in human plasma and, as an acute-phase protein, it has a strong influence on pharmacokinetics and pharmacodynamics of many pharmaceuticals. We report the crystal structure of the recombinant unglycosylated human AGP at 1.8 A resolution, which was solved using the new method of UV-radiation-damage-induced phasing (UV RIP). AGP reveals a typical lipocalin fold comprising an eight-stranded beta-barrel. Of the four loops that form the entrance to the ligand-binding site, loop 1, which connects beta-strands A and B, is among the longest observed so far and exhibits two full turns of an alpha-helix. Furthermore, it carries one of the five N-linked glycosylation sites, while a second one occurs underneath the tip of loop 2. The branched, partly hydrophobic, and partly acidic cavity, together with the presumably flexible loop 1 and the two sugar side chains at its entrance, explains the diverse ligand spectrum of AGP, which is known to vary with changes in glycosylation pattern.
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Rayons ultraviolets
/
Orosomucoïde
/
Diazépam
/
Lipocalines
/
Biologie moléculaire
Limites:
Humans
Langue:
En
Journal:
J Mol Biol
Année:
2008
Type de document:
Article
Pays d'affiliation:
Allemagne