التفاصيل البيبلوغرافية
| العنوان: |
The peptide bond rupture mechanism in the serine proteases: an in silico study based on sequential scale models |
| المؤلفون: |
Díaz Cervantes, Erik, Robles, Juvencio, Solà i Puig, Miquel, Swart, Marcel |
| المساهمون: |
Agencia Estatal de Investigación |
| المصدر: |
© Physical Chemistry Chemical Physics, 2023, vol. 25, p. 8043-8049 ; Articles publicats (D-Q) ; Díaz Cervantes, Erik Robles, Juvencio Solà i Puig, Miquel Swart, Marcel 2023 The peptide bond rupture mechanism in the serine proteases: an in silico study based on sequential scale models Physical Chemistry Chemical Physics 25 8043 8049 |
| بيانات النشر: |
Royal Society of Chemistry (RSC) |
| سنة النشر: |
2023 |
| المجموعة: |
Universitat de Girona: DUGiDocs (UdG Digital Repository) |
| مصطلحات موضوعية: |
Teoria del funcional de densitat, Enzims proteolítics, Density functionals, Proteolytic enzymes, Pèptids, Peptides |
| الوصف: |
Given the importance of serine proteases for biochemical processes, we have studied the peptide bond rupture mechanism using three sequential scale models as representations of the KLK5 enzyme (a protein overexpressed in ovarian cancer). The first model contains the basic functional groups of the residues that conform the catalytic triad present in serine proteases; the second model consists of considering some additional residues and, finally, the last representation includes all atoms of the KLK5 protein together with 10.000 explicit water molecules. This separation into three scale models allows us to separate the intrinsic reactivity of the catalytic triad from the process taking place in the enzyme. The methodologies employed in this work include full DFT calculations with a dielectric continuum in the first two models and a multi-level setup with a Quantum Mechanics/Molecular Mechanics (QM/MM) partition in the whole protein system. Our results show that the peptide-bond rupture mechanism is a stepwise process involving two proton transfer reactions. The rate-determining step is the second proton transfer from the imidazole group to the amidic nitrogen of the substrate. In addition, we find that the simplest model does not provide accurate results compared to the full protein system. This can be attributed to the electronic stabilization conferred by the residues around the reaction site. Interestingly, the energy profile obtained with the second scale model with additional residues shows the same trends as the full system and could therefore be considered an appropriate model system. It could be used for studying the peptide bond rupture mechanism in case full QM/MM calculations cannot be performed, or as a rapid tool for screening purposes ; We thank the Laboratorio Nacional de Caracterización de Propiedades Fisicoquímicas y Estructura Molecular (UG-UAA-CONACYT, Project: 123732) for the computing time provided at the PIPILA cluster, AEI/MCIU (projects PID2020-114548GB-I00 and PID2020-113711GB-I00), the ... |
| نوع الوثيقة: |
article in journal/newspaper |
| وصف الملف: |
7 p.; application/pdf |
| اللغة: |
English |
| Relation: |
info:eu-repo/semantics/altIdentifier/issn/1463-9076; info:eu-repo/semantics/altIdentifier/eissn/1463-9084; PID2020-113711GB-I00; PID2020-114548GB-I00; info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/PID2020-113711GB-I00/ES/DISEÑO Y SINTESIS DE FULLERENOS PARA LA CONSTRUCCION DE CELDAS SOLARES HIBRIDAS DE PEROVSKITA Y FULERENOS D ALTO RENDIMIENTO. UN ENFOQUE EXPERIMENTAL Y COMPUTACIONAL SINERGICO/; info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/PID2020-114548GB-I00/ES/CORRELATING FUNCTIONALITY/; http://hdl.handle.net/10256/22895 |
| الاتاحة: |
http://hdl.handle.net/10256/22895 |
| Rights: |
Tots els drets reservats ; info:eu-repo/semantics/openAccess |
| رقم الانضمام: |
edsbas.16FC6733 |
| قاعدة البيانات: |
BASE |