3INA

Crystal structure of heparin lyase I H151A mutant complexed with a dodecasaccharide heparin

Summary for 3INA

• Entry DOI: 10.2210/pdb3ina/pdb
• Related: 3IMN 3IN9
• Descriptor: Heparin lyase I, 2-deoxy-6-O-sulfo-2-(sulfoamino)-alpha-D-glucopyranose-(1-4)-2-O-sulfo-alpha-L-idopyranuronic acid-(1-4)-2-deoxy-3,6-di-O-sulfo-2-(sulfoamino)-alpha-D-glucopyranose-(1-4)-2-O-sulfo-alpha-L-idopyranuronic acid-(1-4)-2-deoxy-6-O-sulfo-2-(sulfoamino)-alpha-D-glucopyranose-(1-4)-2-O-sulfo-alpha-L-idopyranuronic acid-(1-4)-2-deoxy-6-O-sulfo-2-(sulfoamino)-alpha-D-glucopyranose-(1-4)-2-O-sulfo-alpha-L-idopyranuronic acid, CALCIUM ION, ... (4 entities in total)
• Functional Keywords: jelly roll, lyase
• Biological source: Bacteroides thetaiotaomicron
• Total number of polymer chains: 1
• Total formula weight: 45215.33

Authors

Han, Y.H.,Ryu, K.S.,Kim, H.Y.,Jeon, Y.H. (deposition date: 2009-08-12, release date: 2009-09-29, Last modification date: 2023-11-01)

Primary citation

Han, Y.H.,Garron, M.L.,Kim, H.Y.,Kim, W.S.,Zhang, Z.,Ryu, K.S.,Shaya, D.,Xiao, Z.,Cheong, C.,Kim, Y.S.,Linhardt, R.J.,Jeon, Y.H.,Cygler, M.
Structural snapshots of heparin depolymerization by heparin lyase I
J.Biol.Chem., 284:34019-34027, 2009

PubMed 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.

PubMed: 19801541
DOI: 10.1074/jbc.M109.025338

Experimental method

X-RAY DIFFRACTION (1.9 Å)