Ståhlberg, Jerry
- Department of Molecular Biology, Swedish University of Agricultural Sciences
As part of an ongoing enzyme discovery program to investigate the properties and catalytic mechanism of glycoside hydrolase family 12 (GH 12) endoglucanases, a GH family that contains several cellulases that are of interest in industrial applications, we have solved four new crystal structures of wild-type Humicola grisea Cel12A in complexes formed by soaking with cellobiose, cellotetraose, cellopentaose, and a thio-linked cellotetraose derivative (G(2)SG(2)). These complex structures allow mapping of the non-covalent interactions between the enzyme and the glucosyl chain bound in subsites -4 to +2 of the enzyme, and shed light on the mechanism and function of GH 12 cellulases. The unhydrolysed cellopentaose and the G2SG2 cello-oligomers span the active site of the catalytically active H. grisea Cel12A enzyme, with the pyranoside bound in subsite -1 displaying a S-1(3) skew boat conformation. After soaking in cellotetraose, the cello-oligomer that is found bound in site -4 to -1 contains a beta-1,3-linkage between the two cellobiose units in the oligomer, which is believed to have been formed by a transglycosylation reaction that has occurred during the ligand soak of the protein crystals. The close fit of this ligand and the binding sites occupied suggest a novel mixed beta-glucanase activity for this enzyme. (C) 2004 Elsevier Ltd. All rights reserved.
cellulase; cellulose; endoglucanase; substrate complex; crystal structure
Journal of Molecular Biology
2004, volume: 342, number: 5, pages: 1505-1517
Publisher: ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD
Molecular Biology
https://res.slu.se/id/publ/3263