Proton relay network in P450cam formed upon docking of putidaredoxin

Date

2020-04-01

Author

Ugur, Ilke
Chandrasekhar, Prasanna

Metadata

Show full item record

This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

Item Usage Stats

101
views

0
downloads

Cytochromes P450 are versatile heme-based enzymes responsible for vital life processes. Of these, P450cam (substrate camphor) has been most studied. Despite this, precise mechanisms of the key OO cleavage step remain partly elusive to date; effects observed in various enzyme mutants remain partly unexplained. We have carried out extended (to 1000 ns) MM-MD and follow-on quantum mechanics/molecular mechanics computations, both on the well-studied FeOO state and on Cpd(0) (compound 0). Our simulations include (all camphor-bound): (a) WT (wild type), FeOO state. (b) WT, Cpd(0). (c) Pdx (Putidaredoxin, redox partner of P450)-docked-WT, FeOO state. (d) Pdx-docked WT, Cpd(0). (e) Pdx-docked T252A mutant, Cpd(0). Among our key findings: (a) Effect of Pdx docking appears to go far beyond that indicated in prior studies: it leads to specific alterations in secondary structure that create the crucial proton relay network. (b) Specific proton relay networks we identify are: FeOO(H)MIDLINE HORIZONTAL ELLIPSIST252MIDLINE HORIZONTAL ELLIPSISnH2OMIDLINE HORIZONTAL ELLIPSISD251 in WT; FeOO(H)MIDLINE HORIZONTAL ELLIPSISnH2OMIDLINE HORIZONTAL ELLIPSISD251 in T252A mutant; both occur with Pdx docking. (c) Direct interaction of D251 with -FeOOH is, respectively, rare/frequent in WT/T252A mutant. (d) In WT, T252 is in the proton relay network. (e) Positioning of camphor appears significant: when camphor is part of H-bonding network, second protonation appears to be facilitated.

Subject Keywords

Biochemistry, Molecular Biology, Structural Biology

URI

https://hdl.handle.net/11511/65870

Journal

PROTEINS-STRUCTURE FUNCTION AND BIOINFORMATICS

DOI

https://doi.org/10.1002/prot.25835

Collections

Department of Chemistry, Article

Suggestions

OpenMETU
Core

Immunotherapeutic applications of CpG ODN Gürsel, Mayda (2006-06-01) Bacterial DNA and synthetic oligodeoxynucleotides (ODN) expressing unmethylated CpG motifs stimulate the mammalian immune system to mount a rapid innate immune response. This response is characterized by the production of polyreactive IgM, immunomodulatory cytokines and chemokines. CpG ODN directly stimulate lymphocytes, natural killer cells and professional antigen-presenting cells (such as macrophages and dendritic cells). Owing to the strength and nature of this stimulation, CpG ODN are being harnessed f...
Alpha crystallin domain mutations increase holdase capacity of the archeal small heat shock protein, Tpv HSP 14.3 Kocabıyık, Semra (2016-07-25) Protein stability involves the ability of native, folded protein structure to withstand the disruptive, denaturing effects of the external environment. Proteins used in many medical or biotechnological processes are often subjected to conditions which may trigger their degradation, aggregation or inactivation. Therefore, stabilization of proteins is one of the most challenging tasks that has to be addressed in protein based technologies. Many methods have been proposed for improvement of chemical and/or phy...
DynaDom: structure-based prediction of T cell receptor inter-domain and T cell receptor-peptide-MHC (class I) association angles Hoffmann, Thomas; Marıon, Antoıne; Antes, Iris (Springer Science and Business Media LLC, 2017-02-02) Background: T cell receptor (TCR) molecules are involved in the adaptive immune response as they distinguish between self- and foreign-peptides, presented in major histocompatibility complex molecules (pMHC). Former studies showed that the association angles of the TCR variable domains (Va/V beta) can differ significantly and change upon binding to the pMHC complex. These changes can be described as a rotation of the domains around a general Center of Rotation, characterized by the interaction of two highly...
Impacts of multistressors on the survival and life history traits of Daphnia Pulex Bezirci, Gizem; Beklioğlu, Meryem; Department of Biology (2008) As Daphnia have an important role in freshwater food webs, it is important to understand how environmental stressors affect their survival and life history traits. Daphnia pulex were first acutely exposed to a combination of NaCl salinities (0.00-10.0 g/L) and fish-exuded kairomone. The 24 and 48 hour LC50 values were 0.401 and 0.159 g/L in kairomone-absence and 1.962 and 1.007 g/L in kairomone-presence. Hence, survival decreased with increasing salinity, while the kairomone enhanced daphnid resistance to s...
Immobilization of glucose oxidase in conducting graft copolymers and determination of glucose amount in orange juices with enzyme electrodes Yildiz, HB; Kiralp, S; Toppare, Levent Kamil; Yagci, Y (Elsevier BV, 2005-12-15) Glucose oxidase was immobilized in conducting copolymers of three different types of poly(methyl methacrylate-co-thienyl methacrylate). Immobilization of enzyme was carried out by the entrapment in conducting polymers during electrochemical polymerization of pyrrole on the copolymer electrodes. Maximum reaction rate, Michaelis-Menten constants, temperature, pH and operational stabilities were determined for immobilized enzyme. The amount of glucose in orange juices of Turkey was investigated by using enzyme...

Citation Formats

I. Ugur and P. Chandrasekhar, “Proton relay network in P450cam formed upon docking of putidaredoxin,” PROTEINS-STRUCTURE FUNCTION AND BIOINFORMATICS, pp. 558–572, 2020, Accessed: 00, 2020. [Online]. Available: https://hdl.handle.net/11511/65870.