ArticleThe Journal of biological chemistry2013
Systems-level modeling with molecular resolution elucidates the rate-limiting mechanisms of cellulose decomposition by cellobiohydrolases.
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed.
- Are cellulases slow? Kinetic and thermodynamic limitations for enzymatic breakdown of cellulose.BBA advances · 2025Review
- Impact of Synergy Partner Cel7B on Cel7A Binding Rates: Insights from Single-Molecule Data.The journal of physical chemistry. B · 2024Article
- Model of Processive Catalysis with Site Clustering and Blocking and Its Application to Cellulose Hydrolysis.The journal of physical chemistry. B · 2022Article
- Modeling the activity burst in the initial phase of cellulose hydrolysis by the processive cellobiohydrolase Cel7A.Biotechnology and bioengineering · 2019Article
- Development of modified HCH-1 kinetic model for long-term enzymatic cellulose hydrolysis and comparison with literature models.Biotechnology for biofuels · 2019Article
- Alanine substitution in cellobiohydrolase provides new insights into substrate threading.Scientific reports · 2017Article
- Inter-domain Synergism Is Required for Efficient Feeding of Cellulose Chain into Active Site of Cellobiohydrolase Cel7A.The Journal of biological chemistry · 2016Article
- Cellular automata modeling depicts degradation of cellulosic material by a cellulase system with single-molecule resolution.Biotechnology for biofuels · 2016Article
- Slow Off-rates and Strong Product Binding Are Required for Processivity and Efficient Degradation of Recalcitrant Chitin by Family 18 Chitinases.The Journal of biological chemistry · 2015Article
- Free Energy Diagram for the Heterogeneous Enzymatic Hydrolysis of Glycosidic Bonds in Cellulose.The Journal of biological chemistry · 2015Article
- The predominant molecular state of bound enzyme determines the strength and type of product inhibition in the hydrolysis of recalcitrant polysaccharides by processive enzymes.The Journal of biological chemistry · 2015Article
- Kinetics of cellobiohydrolase (Cel7A) variants with lowered substrate affinity.The Journal of biological chemistry · 2014Article
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3 authors.
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Abstract
Interprotein and enzyme-substrate couplings in interfacial biocatalysis induce spatial correlations beyond the capabilities of classical mass-action principles in modeling reaction kinetics. To understand the impact of spatial constraints on enzyme kinetics, we developed a computational scheme to simulate the reaction network of enzymes with the structures of individual proteins and substrate molecules explicitly resolved in the three-dimensional space. This methodology was applied to elucidate the rate-limiting mechanisms of crystalline cellulose decomposition by cellobiohydrolases. We illustrate that the primary bottlenecks are slow complexation of glucan chains into the enzyme active site and excessive enzyme jamming along the crowded substrate. Jamming could be alleviated by increasing the decomplexation rate constant but at the expense of reduced processivity. We demonstrate that enhancing the apparent reaction rate required a subtle balance between accelerating the complexation driving force and simultaneously avoiding enzyme jamming. Via a spatiotemporal systems analysis, we developed a unified mechanistic framework that delineates the experimental conditions under which different sets of rate-limiting behaviors emerge. We found that optimization of the complexation-exchange kinetics is critical for overcoming the barriers imposed by interfacial confinement and accelerating the apparent rate of enzymatic cellulose decomposition.
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