Structural snapshots of heparin depolymerization by heparin lyase I
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Authors
Han, Young Hyun
Garron, Marie Line
Kim, Hye Yeon
Kim, Wan Seok
Zhang, Zhenqing
Ryu, Kyeong Seok
Shaya, David
Xiao, Zhongping
Cheong, Chaejoon
Kim, Yeong Shik
Issue Date
2009-12-04
Type
Article
Language
en_US
Keywords
Biology , Chemistry and chemical biology , Chemical and biological engineering , Biomedical engineering
Alternative Title
Abstract
Heparin lyase I (heparinase I) specifically depolymerizes heparin, cleaving the glycosidic linkage next to iduronic acid. Here, we show the crystal structures of heparinase I from Bacteroides thetaiotaomicron at various stages of the reaction with heparin oligosaccharides before and just after cleavage and product disaccharide. The heparinase I structure is comprised of a beta-jellyroll domain harboring a long and deep substrate binding groove and an unusual thumb-resembling extension. This thumb, decorated with many basic residues, is of particular importance in activity especially on short heparin oligosaccharides. Unexpected structural similarity of the active site to that of heparinase II with an (alpha/alpha)(6) fold is observed. Mutational studies and kinetic analysis of this enzyme provide insights into the catalytic mechanism, the substrate recognition, and processivity.
Description
Journal of Biological Chemistry, 284, 34019–34027
Note : if this item contains full text it may be a preprint, author manuscript, or a Gold OA copy that permits redistribution with a license such as CC BY. The final version is available through the publisher’s platform.
Note : if this item contains full text it may be a preprint, author manuscript, or a Gold OA copy that permits redistribution with a license such as CC BY. The final version is available through the publisher’s platform.
Full Citation
Structural snapshots of heparin depolymerization by heparin lyase I, Y.-H. Han, M.-L. Garron, H.-Y. Kim, W.-S. Kim, Z. Zhang, K.-S. Ryu, D. Shaya, Z. Xiao, C. Cheong, Y.-S. Kim, R. J. Linhardt, Y. H. Jeon, M. Cygler, Journal of Biological Chemistry, 284, 34019–34027, 2009.
Publisher
Elsevier
Terms of Use
Journal
Volume
Issue
PubMed ID
DOI
ISSN
1083351X
219258
219258