Structural highlights
Function
[A1AG1_HUMAN] Functions as transport protein in the blood stream. Binds various ligands in the interior of its beta-barrel domain. Also binds synthetic drugs and influences their distribution and availability in the body. Appears to function in modulating the activity of the immune system during the acute-phase reaction.[1] [2]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
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.
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.,Schonfeld DL, Ravelli RB, Mueller U, Skerra A J Mol Biol. 2008 Dec 12;384(2):393-405. Epub 2008 Sep 16. PMID:18823996[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Fitos I, Visy J, Zsila F, Mady G, Simonyi M. Selective binding of imatinib to the genetic variants of human alpha1-acid glycoprotein. Biochim Biophys Acta. 2006 Nov;1760(11):1704-12. Epub 2006 Aug 25. PMID:17008009 doi:10.1016/j.bbagen.2006.08.015
- ↑ Zsila F, Iwao Y. The drug binding site of human alpha1-acid glycoprotein: insight from induced circular dichroism and electronic absorption spectra. Biochim Biophys Acta. 2007 May;1770(5):797-809. Epub 2007 Jan 28. PMID:17321687 doi:10.1016/j.bbagen.2007.01.009
- ↑ Schonfeld DL, Ravelli RB, Mueller U, Skerra A. 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. 2008 Dec 12;384(2):393-405. Epub 2008 Sep 16. PMID:18823996 doi:10.1016/j.jmb.2008.09.020
