Year: 2011
Type: article
Abstract: Chondroitin, heparin/heparan and hyaluronan are the primary glycosaminoglycans found in humans and are linear polysaccharides consisting of an amino sugar and an uronic acid.Chondroitin chains range from 40 to over 100 repeating units of the disaccharide (GlcUA β (1-3)-GalNAc β (1-4)).Sulfated chondroitins are involved in the regulation of various biological functions such as central nervous system development, wound repair, infection, growth factor signaling, and morphogenesis, in addition to its conventional structural roles.Elongation of glycosaminoglycan chains is catalyzed by bi-functional glycosyltransferases.The bacterial chondroitin polymerase K4CP catalyzes elongation of the chondroitin chain by alternatively transferring the GlcUA and GalNAc moiety from UDP-GlcUA and UDP-GalNAc to the nonreducing ends of the chondroitin chain [1].We previously reported the crystal structure of K4CP in the presence of UDP and UDP-GalNAc as well as with UDP and UDP-GlcUA [2].The structures consisted of two GT-A fold domains in which the two active sites were 60Å apart.UDP-GalNAc and UDP-GlcUA were found at the active sites of the N-terminal and C-terminal domains, respectively.Here, we present the crystal structure of K4CP complexed with chondroitin hexamer (CH6) and UDP at 3.5Å resolution.CH6 was found at the active sites of the N-terminal domain.In addition, we generated docking model of the C-terminal domain with chondroitin pentamer.These structural information revealed molecular basis of catalysis and substrate recognition, and provided the structural basis for further investigating the molecular mechanism of biosynthesis of chondroitin chain.
Authors: M. Soejima, N. Sugiura, M. Sobhany, K. Kimata, M. Negishi, M. Kimura, Y. Kakuta
Institutions: Kyushu University, SLAC National Accelerator Laboratory, Joint Center for Structural Genomics, Stanford Synchrotron Radiation Lightsource, Scripps Research Institute, Seikagaku Corporation (Japan), Institute for Molecular Science of Medicine, Aichi Medical University, National Institutes of Health, National Institute of Environmental Health Sciences
Language: English
Subfield: Cell Biology
Domain: Life Sciences
Open Access status: bronze
OpenAlex ID: W2322095696