Taxonomic group: fungi / Ascomycota
(Phylum: Ascomycota)
NCBI PubMed ID: 24942743Publication DOI: 10.1074/jbc.M114.563353Journal NLM ID: 2985121RPublisher: Baltimore, MD: American Society for Biochemistry and Molecular Biology
Correspondence: Dorfmueller HC <hczdorfmueller

dundee.ac.uk>; van Aalten DM <dmfvanaalten

dundee.ac.uk>
Institutions: Division of Molecular Microbiology, College of Life Sciences, University of Dundee, Dundee, UK, MRC Protein Phosphorylation and Ubiquitylation Unit, College of Life Sciences, University of Dundee, Dundee, UK
Chitin synthases (CHS) produce chitin, an essential component of the fungal cell wall. The molecular mechanism of processive chitin synthesis is not understood, limiting the discovery of new inhibitors of this enzyme class. We identified the bacterial glycosyltransferase NodC as an appropriate model system to study the general structure and reaction mechanism of CHS. A high throughput screening-compatible novel assay demonstrates that a known inhibitor of fungal CHS also inhibit NodC. A structural model of NodC, on the basis of the recently published BcsA cellulose synthase structure, enabled probing of the catalytic mechanism by mutagenesis, demonstrating the essential roles of the DD and QXXRW catalytic motifs. The NodC membrane topology was mapped, validating the structural model. Together, these approaches give insight into the CHS structure and mechanism and provide a platform for the discovery of inhibitors for this antifungal target.
cell wall, chitin, chitin synthase
Structure type: homopolymer
Location inside paper: abstract
Trivial name: chitin
Compound class: O-polysaccharide, cell wall polysaccharide, glucan, polysaccharide, chitin
Contained glycoepitopes: IEDB_135813,IEDB_137340,IEDB_141807,IEDB_151531,IEDB_153212,IEDB_241099,IEDB_423114,IEDB_423150,SB_74,SB_85
Methods: DNA techniques, enzymatic assays
Biological activity: Exerts antifungal activities versus Candida albicans.
Enzymes that release or process the structure: chitooligosaccharide synthase NodC
Related record ID(s): 40517, 43385, 101632, 118702, 139869, 143703, 145244, 147175, 149428, 149871, 149874
NCBI Taxonomy refs (TaxIDs): 4932Reference(s) to other database(s): GTC:G97099AY, CCSD:
46067, CBank-STR:5851, GenDB:KF905651
Show glycosyltransferases
There is only one chemically distinct structure: