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Title: Strategies to reduce end-product inhibition in family 48 glycoside hydrolases

Journal Article · · Proteins
DOI:https://doi.org/10.1002/prot.24965· OSTI ID:1240085
 [1];  [2];  [2];  [2];  [2];  [2];  [1];  [2];  [2];  [2]
  1. Cornell Univ., Ithaca, NY (United States)
  2. National Renewable Energy Lab. (NREL), Golden, CO (United States)
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Family 48 cellobiohydrolases are some of the most abundant glycoside hydrolases in nature. They are able to degrade cellulosic biomass and therefore serve as good enzyme candidates for biofuel production. Family 48 cellulases hydrolyze cellulose chains via a processive mechanism, and produce end products composed primarily of cellobiose as well as other cellooligomers (dp ≤ 4). The challenge of utilizing cellulases in biofuel production lies in their extremely slow turnover rate. A factor contributing to the low enzyme activity is suggested to be product binding to enzyme and the resulting performance inhibition. In this study, we quantitatively evaluated the product inhibitory effect of four family 48 glycoside hydrolases using molecular dynamics simulations and product expulsion free-energy calculations. We also suggested a series of single mutants of the four family 48 glycoside hydrolases with theoretically reduced level of product inhibition. As a result, the theoretical calculations provide a guide for future experimental studies designed to produce mutant cellulases with enhanced activity.

Research Organization:
National Renewable Energy Laboratory (NREL), Golden, CO (United States)
Sponsoring Organization:
USDOE Office of Science (SC)
Grant/Contract Number:
AC36-08GO28308
OSTI ID:
1240085
Report Number(s):
NREL/JA-2700-65427
Journal Information:
Proteins, Vol. 84, Issue 3; Related Information: Proteins: Structure, Function, and Bioinformatics; ISSN 0887-3585
Publisher:
WileyCopyright Statement
Country of Publication:
United States
Language:
English
Citation Metrics:
Cited by: 8 works
Citation information provided by
Web of Science

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Cited By (2)

Natural diversity of glycoside hydrolase family 48 exoglucanases: insights from structure journal November 2017
Determination of the native features of the exoglucanase Cel48S from Clostridium thermocellum journal January 2018

Figures / Tables (9)

Table I(p. 25)table Table I
Table II(p. 26)table Table II
Table III(p. 27)table Table III
Figure 1(p. 28)figure Figure 1
Figure 2(p. 29)figure Figure 2
Figure 3(p. 30)figure Figure 3
Figure 4(p. 31)figure Figure 4
Figure 5(p. 32)figure Figure 5
Figure 6(p. 33)figure Figure 6

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Related Subjects

09 BIOMASS FUELS
59 BASIC BIOLOGICAL SCIENCES
glycoside hydrolases
product inhibition
biofuels
cellulose
molecular dynamics