期刊
JOURNAL OF MOLECULAR BIOLOGY
卷 384, 期 2, 页码 393-405出版社
ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
DOI: 10.1016/j.jmb.2008.09.020
关键词
acute-phase protein; ligand binding; protein engineering; UV-radiation-damage-induced phasing; X-ray crystallography
资金
- Munich Center for Integrated Protein Science
- Deutsche Forschungsgemeinschaft
- European Synchrotron Radiation Facility [ID23-1]
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 angstrom resolution, which was solved using the new method of UV-radiation-damage-incluced 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. (C) 2008 Elsevier Ltd. All rights reserved.
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