4D5P

Hypocrea jecorina cellobiohydrolase Cel7A E217Q soaked with xylopentaose.

Summary for 4D5P

• Entry DOI: 10.2210/pdb4d5p/pdb
• Related: 4D5I 4D5J 4D5O 4D5Q 4D5V
• Descriptor: CELLULOSE 1,4-BETA-CELLOBIOSIDASE, beta-D-xylopyranose-(1-4)-beta-D-xylopyranose-(1-4)-beta-D-xylopyranose-(1-4)-beta-D-xylopyranose, COBALT (II) ION, ... (5 entities in total)
• Functional Keywords: hydrolase, glycoside hydrolase, cellobiohydrolase, cellulase. inhibition, xylooligosaccharides
• Biological source: TRICHODERMA REESEI QM9414
• Total number of polymer chains: 1
• Total formula weight: 46953.30

Authors

Momeni, M.H.,Ubhayasekera, W.,Stahlberg, J.,Hansson, H. (deposition date: 2014-11-07, release date: 2015-03-25, Last modification date: 2023-12-20)

Primary citation

Haddad Momeni, M.,Ubhayasekera, W.,Sandgren, M.,Stahlberg, J.,Hansson, H.
Structural Insights Into the Inhibition of Cellobiohydrolase Cel7A by Xylooligosaccharides.
FEBS J., 282:2167-, 2015

PubMed Abstract: The filamentous fungus Hypocrea jecorina (anamorph of Trichoderma reesei) is the predominant source of enzymes for industrial saccharification of lignocellulose biomass. The major enzyme, cellobiohydrolase Cel7A, constitutes nearly half of the total protein in the secretome. The performance of such enzymes is susceptible to inhibition by compounds liberated by physico-chemical pre-treatment if the biomass is kept unwashed. Xylan and xylo-oligosaccharides (XOS) have been proposed to play a key role in inhibition of cellobiohydrolases of glycoside hydrolase family 7. To elucidate the mechanism behind this inhibition at a molecular level, we used X-ray crystallography to determine structures of H. jecorina Cel7A in complex with XOS. Structures with xylotriose, xylotetraose and xylopentaose revealed a predominant binding mode at the entrance of the substrate-binding tunnel of the enzyme, in which each xylose residue is shifted ~ 2.4 Å towards the catalytic center compared with binding of cello-oligosaccharides. Furthermore, partial occupancy of two consecutive xylose residues at subsites -2 and -1 suggests an alternative binding mode for XOS in the vicinity of the catalytic center. Interestingly, the -1 xylosyl unit exhibits an open aldehyde conformation in one of the structures and a ring-closed pyranoside in another complex. Complementary inhibition studies with p-nitrophenyl lactoside as substrate indicate mixed inhibition rather than pure competitive inhibition.

PubMed: 25765184
DOI: 10.1111/FEBS.13265

Experimental method

X-RAY DIFFRACTION (1.89 Å)