6LJL

Crystal Structure of exoHep-Y390A/H555A complexed with a tetrasaccharide substrate

Summary for 6LJL

• Entry DOI: 10.2210/pdb6ljl/pdb
• Descriptor: Heparinase II/III-like protein, 4-deoxy-alpha-L-threo-hex-4-enopyranuronic 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, CALCIUM ION, ... (4 entities in total)
• Functional Keywords: heparin, heparan sulfate, heparinase, crystall, lyase
• Biological source: Bacteroides intestinalis DSM 17393
• Total number of polymer chains: 1
• Total formula weight: 101053.33

Authors

Zhang, Q.D.,Cao, H.Y.,Wei, L.,Li, F.C.,Zhang, Y.Z. (deposition date: 2019-12-17, release date: 2020-12-23, Last modification date: 2023-11-22)

Primary citation

Zhang, Q.,Cao, H.Y.,Wei, L.,Lu, D.,Du, M.,Yuan, M.,Shi, D.,Chen, X.,Wang, P.,Chen, X.L.,Chi, L.,Zhang, Y.Z.,Li, F.
Discovery of exolytic heparinases and their catalytic mechanism and potential application.
Nat Commun, 12:1263-1263, 2021

PubMed Abstract: Heparinases (Hepases) are critical tools for the studies of highly heterogeneous heparin (HP)/heparan sulfate (HS). However, exolytic heparinases urgently needed for the sequencing of HP/HS chains remain undiscovered. Herein, a type of exolytic heparinases (exoHepases) is identified from the genomes of different bacteria. These exoHepases share almost no homology with known Hepases and prefer to digest HP rather than HS chains by sequentially releasing unsaturated disaccharides from their reducing ends. The structural study of an exoHepase (BIexoHep) shows that an N-terminal conserved DUF4962 superfamily domain is essential to the enzyme activities of these exoHepases, which is involved in the formation of a unique L-shaped catalytic cavity controlling the sequential digestion of substrates through electrostatic interactions. Further, several HP octasaccharides have been preliminarily sequenced by using BIexoHep. Overall, this study fills the research gap of exoHepases and provides urgently needed tools for the structural and functional studies of HP/HS chains.

PubMed: 33627653
DOI: 10.1038/s41467-021-21441-8

Experimental method

X-RAY DIFFRACTION (1.73 Å)