Fine-Tuning of Sequence Specificity by Near Attack Conformations in Enzyme-Catalyzed Peptide Hydrolysis
Abstract
:1. Introduction
2. Results
2.1. Differential Nucleophilic Water Binding
2.2. Analysis of the Hydrogen Bond Network
2.3. Thermodynamic Decomposition of Activation Free Energy Contributions
3. Discussion
4. Materials and Methods
4.1. Initial Preparation
4.2. Molecular Dynamics Equilibration and Production Simulation Protocol
4.3. Analysis
5. Conclusions
Funding
Acknowledgments
Conflicts of Interest
References
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System | Cleavage Sequence | (Å) | G |
---|---|---|---|
MA-CA | SGNY-PIVQ | 4.6 | −0.4 ± 0.1 |
CA-SP1 | ARVL-AEAM | 4.2 | −1.9 ± 0.5 |
SP1-NC | ATIM-MQRG | 4.6 | −1.0 ± 0.1 |
NC-SP2 | RQAN-FLGK | 4.6 | −1.1 ± 0.3 |
SP2-p6 | PYNF-LQSR | 4.6 | −3.7 ± 1.2 |
TFR-PR | SFNF-PQIT | 4.6 | −0.4 ± 0.2 |
PR-RT | TLNF-PISP | 4.6 | 2.0 ± 0.3 |
RT-RH | AETP-YVDG | 4.6 | −0.1 ± 0.2 |
RH-IN | RKIL-FLDG | 4.6 | −2.2 ± 0.7 |
Uncatalyzed | Catalyzed | ||||||||
---|---|---|---|---|---|---|---|---|---|
System | G | G | G | G | G | G | G | G | G |
MA-CA | ∼30 | 3.8 ± 0.1 | 26.2 | 15.7 | 2.1 ± 0.1 | 13.6 | −14.3 | −1.7 ± 0.2 | −12.6 |
CA-SP1 | 4.4 ± 0.1 | 25.6 | 17.0 | 3.7 ± 0.2 | 13.3 | −13.0 | −0.7 ± 0.3 | −12.3 | |
SP1-NC | 4.6 ± 0.1 | 25.4 | 15.3 | 4.6 ± 0.2 | 10.7 | −14.7 | 0.0 ± 0.3 | −14.7 | |
NC-SP2 | 4.3 ± 0.1 | 25.7 | 16.7 | 3.8 ± 0.2 | 12.9 | −13.3 | −0.5 ± 0.3 | −12.8 | |
SP2-p6 | 4.8 ± 0.3 | 25.2 | 18.4 | 3.1 ± 0.1 | 15.3 | −11.6 | −1.7 ± 0.4 | −9.9 | |
TFR-PR | 4.1 ± 0.1 | 25.9 | 15.3 | 1.9 ± 0.2 | 13.4 | −14.7 | −2.2 ± 0.3 | −12.5 | |
PR-RT | 3.9 ± 0.1 | 26.1 | 15.8 | 4.2 ± 0.5 | 11.6 | −14.2 | 0.3 ± 0.6 | −14.5 | |
RT-RH | 4.7 ± 0.4 | 25.3 | 17.2 | 3.7 ± 0.4 | 13.5 | −12.8 | −1.0 ± 0.8 | −11.8 | |
RH-IN | 4.4 ± 0.1 | 25.6 | 16.6 | 3.5 ± 0.1 | 13.1 | −13.4 | −0.9 ± 0.2 | −12.5 |
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Sadiq, S.K. Fine-Tuning of Sequence Specificity by Near Attack Conformations in Enzyme-Catalyzed Peptide Hydrolysis. Catalysts 2020, 10, 684. https://doi.org/10.3390/catal10060684
Sadiq SK. Fine-Tuning of Sequence Specificity by Near Attack Conformations in Enzyme-Catalyzed Peptide Hydrolysis. Catalysts. 2020; 10(6):684. https://doi.org/10.3390/catal10060684
Chicago/Turabian StyleSadiq, S. Kashif. 2020. "Fine-Tuning of Sequence Specificity by Near Attack Conformations in Enzyme-Catalyzed Peptide Hydrolysis" Catalysts 10, no. 6: 684. https://doi.org/10.3390/catal10060684
APA StyleSadiq, S. K. (2020). Fine-Tuning of Sequence Specificity by Near Attack Conformations in Enzyme-Catalyzed Peptide Hydrolysis. Catalysts, 10(6), 684. https://doi.org/10.3390/catal10060684