1T8U

Crystal Structure of human 3-O-Sulfotransferase-3 with bound PAP and tetrasaccharide substrate

Summary for 1T8U

• Entry DOI: 10.2210/pdb1t8u/pdb
• Related: 1BFB 1HY3 1S6T 1T8T
• Descriptor: heparan sulfate D-glucosaminyl 3-O-sulfotransferase 3A1, 4-deoxy-2-O-sulfo-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, SULFATE ION, ... (6 entities in total)
• Functional Keywords: alpha-beta motif, substrate-binding cleft, transferase
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 2
• Total formula weight: 64409.16

Authors

Moon, A.F.,Edavettal, S.C.,Krahn, J.M.,Munoz, E.M.,Negishi, M.,Linhardt, R.J.,Liu, J.,Pedersen, L.C. (deposition date: 2004-05-13, release date: 2004-08-31, Last modification date: 2024-10-09)

Primary citation

Moon, A.F.,Edavettal, S.C.,Krahn, J.M.,Munoz, E.M.,Negishi, M.,Linhardt, R.J.,Liu, J.,Pedersen, L.C.
Structural analysis of the sulfotransferase (3-o-sulfotransferase isoform 3) involved in the biosynthesis of an entry receptor for herpes simplex virus 1
J.Biol.Chem., 279:45185-45193, 2004

PubMed Abstract: Heparan sulfate (HS) plays essential roles in assisting herpes simplex virus infection and other biological processes. The biosynthesis of HS includes numerous specialized sulfotransferases that generate a variety of sulfated saccharide sequences, conferring the selectivity of biological functions of HS. We report a structural study of human HS 3-O-sulfotransferase isoform 3 (3-OST-3), a key sulfotransferase that transfers a sulfuryl group to a specific glucosamine in HS generating an entry receptor for herpes simplex virus 1. We have obtained the crystal structure of 3-OST-3 at 1.95 A in a ternary complex with 3'-phosphoadenosine 5'-phosphate and a tetrasaccharide substrate. Mutational analyses were also performed on the residues involved in the binding of the substrate. Residues Gln255 and Lys368 are essential for the sulfotransferase activity and lie within hydrogen bonding distances to the carboxyl and sulfo groups of the uronic acid unit. These residues participate in the substrate recognition of 3-OST-3. This structure provides atomic level evidence for delineating the substrate recognition and catalytic mechanism for 3-OST-3.

PubMed: 15304505
DOI: 10.1074/jbc.M405013200

Experimental method

X-RAY DIFFRACTION (1.95 Å)