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Dissecting the Stru...
Dissecting the Structural Plasticity and Dynamics of Cytochrome P450 2B4 by Molecular Dynamics Simulations
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- Li, Junhao, 1989- (författare)
- KTH,Teoretisk kemi och biologi
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- Zhou, Yang, 1989- (författare)
- KTH,Teoretisk kemi och biologi
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- Tang, Yun (författare)
- East China University of Science and Technology
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visa fler...
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- Li, Weihua (författare)
- East China University of Science and Technology
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- Tu, Yaoquan (författare)
- KTH,Teoretisk kemi och biologi
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visa färre...
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(creator_code:org_t)
- Engelska.
- Relaterad länk:
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https://urn.kb.se/re...
Abstract
Ämnesord
Stäng
- The plasticity of cytochrome P450 enzymes (P450s) is known to contribute significantly to their catalytic capacity of metabolizing various substrates. Although numerous studies have been performed, factors governing the plasticity and dynamics of P450s are still not fully understood. In this study, taking CYP2B4 as an example, we dissect the protein plasticity and dynamics in different environments. CYP2B4 is featured by a high degree of plasticity that exhibits open, closed, and intermediate states. By analyzing the CYP2B4 crystal structures, we identified the structural features for the closed, open and intermediate states. Interestingly, formation of the dimer structure was found in the open and intermediate structures. The subsequent MD simulations of the open structure in water confirmed the importance of the dimer form in stabilizing the open conformations. MD simulations of the closed and open structures in the membrane environment and the free energies for opening the F-G cassette obtained from the umbrella sampling calculations indicate that the membrane environment is important for stabilizing the F-G cassette. The dynamical network analysis indicates that Asp105 on the B-C loop plays an important role in transiting the structure from the open to intermediate. Our results thus unveil the mechanism of dimer formation and open-to-intermediate transition for CYP2B4 in the water and membrane environments.
Ämnesord
- NATURVETENSKAP -- Kemi -- Teoretisk kemi (hsv//swe)
- NATURAL SCIENCES -- Chemical Sciences -- Theoretical Chemistry (hsv//eng)
- NATURVETENSKAP -- Biologi -- Annan biologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Other Biological Topics (hsv//eng)
Nyckelord
- P450
- Conformational plasticity
- Molecular dynamics
- CYP2B4
- Umbrella sampling
Publikations- och innehållstyp
- vet (ämneskategori)
- ovr (ämneskategori)