PUBLICATION
Structure Based Substrate Specificity Analysis of Heparan Sulfate 6-O-Sulfotransferases
- Authors
- Xu, Y., Moon, A.F., Xu, S., Krahn, J.M., Liu, J., Pedersen, L.C.
- ID
- ZDB-PUB-170223-8
- Date
- 2017
- Source
- ACS Chemical Biology 12: 73-82 (Journal)
- Registered Authors
- Keywords
- none
- MeSH Terms
-
- Zebrafish Proteins/chemistry
- Zebrafish Proteins/metabolism
- Sequence Alignment
- Animals
- Sulfotransferases/chemistry
- Sulfotransferases/metabolism*
- Adenosine Diphosphate/chemistry
- Adenosine Diphosphate/metabolism*
- Amino Acid Sequence
- Oligosaccharides/chemistry
- Oligosaccharides/metabolism*
- Zebrafish/metabolism
- Protein Isoforms/chemistry
- Protein Isoforms/metabolism
- Catalytic Domain
- Humans
- Models, Molecular
- Crystallography, X-Ray
- Substrate Specificity
- Protein Conformation
- PubMed
- 28103688 Full text @ ACS Chem. Biol.
Citation
Xu, Y., Moon, A.F., Xu, S., Krahn, J.M., Liu, J., Pedersen, L.C. (2017) Structure Based Substrate Specificity Analysis of Heparan Sulfate 6-O-Sulfotransferases. ACS Chemical Biology. 12:73-82.
Abstract
Heparan sulfate (HS) is a sulfated polysaccharide exhibiting essential physiological functions. HS 6-O-sulfotransferase (6-OST) transfers a sulfo group to the 6-OH position of glucosamine units to confer a variety of HS biological activities. There are three different isoforms of 6-OST in the human genome. Here, we report crystal structures of the ternary complex of 6-OST with the sulfo donor analog 3'-phosphoadenosine 5'-phosphate and three different oligosaccharide substrates at 1.95 to 2.1 Å resolutions. Structural and mutational analyses reveal amino acid residues that contribute to catalysis and substrate recognition of 6-OST. Unexpectedly, the structures reveal 6-OST engages HS in a completely different orientation than other HS sulfotransferases and sheds light on the basic HS requirements for specificity. These findings also contribute structural information to understand mutations in human 6-OST isoform 1 associated with the human genetic disease idiopathic hypogonadotropic hypogonadism characterized by incomplete or lack of puberty.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping