Publications by authors named "Vivian David Jacob"

7 Publications

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Validating the predictions of murburn model for oxygenic photosynthesis: Analyses of ligand-binding to protein complexes and cross-system comparisons.

J Biomol Struct Dyn 2021 Jul 30:1-33. Epub 2021 Jul 30.

RedOx Lab, Department of Life Sciences, Satyamjayatu: The Science & Ethics Foundation, Palakkad District, Kerala, India.

In this second half of our treatise on oxygenic photosynthesis, we provide support for the murburn model of the light reaction of photosynthesis and ratify key predictions made in the first part. Molecular docking and visualization of various ligands of quinones/quinols (and their derivatives) with PS II/Cytochrome complexes did not support chartered 2e-transport role of quinols. A broad variety of herbicides did not show any affinity/binding-based rationales for inhibition of photosynthesis. We substantiate the proposal that disubstituted phenolics (perceived as protonophores/uncouplers or affinity-based inhibitors in the classical purview) serve as interfacial modulators of diffusible reactive (oxygen) species or DR(O)S. The DRS-based murburn model is evidenced by the identification of multiple ADP-binding sites on the extra-membraneous projection of protein complexes and structure/distribution of the photo/redox catalysts. With a panoramic comparison of the redox metabolic machinery across diverse organellar/cellular systems, we highlight the ubiquitous one-electron murburn facets (cofactors of porphyrin, flavin, FeS, other metal centers and photo/redox active pigments) that enable a facile harnessing of the utility of DRS. In the summative analyses, it is demonstrated that the murburn model of light reaction explains the structures of membrane supercomplexes recently observed in thylakoids and also accounts for several photodynamic experimental observations and evolutionary considerations. , the work provides a new orientation and impetus to photosynthesis research. Communicated by Ramaswamy H. Sarma.
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http://dx.doi.org/10.1080/07391102.2021.1953607DOI Listing
July 2021

Structure-function correlations and system dynamics in oxygenic photosynthesis: classical perspectives and murburn precepts.

J Biomol Struct Dyn 2021 Jul 29:1-27. Epub 2021 Jul 29.

Satyamjayatu: The Science & Ethics Foundation, Kulappully, Kerala, India.

Highlights: Contemporary beliefs on oxygenic photosynthesis are critiqued.Murburn model is suggested as an alternative explanation.In the new model, diffusible reactive species are the main protagonists.All pigments are deemed photo-redox active in the new stochastic mechanism.NADPH synthesis occurs via simple electron transfers, not via elaborate ETC.Oxygenesis is delocalized and not just centered at Mn-Complex.Energetics of murburn proposal for photophosphorylation is provided.The proposal ushers in a paradigm shift in photosynthesis research.
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http://dx.doi.org/10.1080/07391102.2021.1953606DOI Listing
July 2021

Hemoglobin catalyzes ATP-synthesis in human erythrocytes: a murburn model.

J Biomol Struct Dyn 2021 May 17:1-13. Epub 2021 May 17.

Satyamjayatu: The Science & Ethics Foundation, Kulappully, India.

Blood hemoglobin (Hb), known to transport oxygen, is the most abundant globular protein in humans. Erythrocytes have ∼10 M concentration of ATP in steady-state and we estimate that this high amounts cannot be formed from 10 - 10 M levels of precursors via substrate-level phosphorylation of glycolysis. To account for this discrepancy, we propose that Hb serves as a 'murzyme' (a redox enzyme working along the principles of murburn concept), catalyzing the synthesis of the major amounts of ATP found in erythrocytes. This proposal is along the lines of our earlier works demonstrating DROS (diffusible reactive oxygen species) mediated ATP-synthesis as a thermodynamically and kinetically viable mechanism for physiological oxidative phosphorylation. We support the new hypothesis for Hb with theoretical arguments, experimental findings of reputed peers and in silico explorations. Using in silico methods, we demonstrate that adenosine nucleotide and 2,3-bisphosphoglycerate (2,3-BPG) binding sites are located suitably on the monomer/tetramer, thereby availing facile access to the superoxide emanating from the heme center. Our proposal explains earlier reported in situ experimental findings/suggestions of 2,3-BPG and ADP binding at the same locus on Hb. The binding energy is in the order of 2,3-BPG > NADH > ATP > ADP > AMP and agrees with earlier reports, potentially explaining the bioenergetic physiology of erythrocytes. Also, the newly discovered site for 2,3-BPG shows lower affinity in fetal Hb (as compared to adults) explaining oxygen transfer from mother to embryo. The findings pose significant implications in routine physiology and pathologies like sickle cell anemia and thalassemia.Communicated by Ramaswamy H. Sarma.
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http://dx.doi.org/10.1080/07391102.2021.1925592DOI Listing
May 2021

Acute toxicity of cyanide in aerobic respiration: Theoretical and experimental support for murburn explanation.

Biomol Concepts 2020 Mar 17;11(1):32-56. Epub 2020 Mar 17.

Department of Biosciences and Bioengineering, Indian Institute of Technology Guwahati, Guwahati, Assam, India-781039.

The inefficiency of cyanide/HCN (CN) binding with heme proteins (under physiological regimes) is demonstrated with an assessment of thermodynamics, kinetics, and inhibition constants. The acute onset of toxicity and CN's mg/Kg LD50 (μM lethal concentration) suggests that the classical hemeFe binding-based inhibition rationale is untenable to account for the toxicity of CN. In vitro mechanistic probing of CN-mediated inhibition of hemeFe reductionist systems was explored as a murburn model for mitochondrial oxidative phosphorylation (mOxPhos). The effect of CN in haloperoxidase catalyzed chlorine moiety transfer to small organics was considered as an analogous probe for phosphate group transfer in mOxPhos. Similarly, inclusion of CN in peroxidase-catalase mediated one-electron oxidation of small organics was used to explore electron transfer outcomes in mOxPhos, leading to water formation. The free energy correlations from a Hammett study and IC50/Hill slopes analyses and comparison with ligands ( CO/ H 2 S/ N 3 - ) $\left( {\text{CO}}/{{{{\text{H}}_{2}}\text{S}}/{\text{N}_{3}^{\text{-}}}\;}\; \right)$ provide insights into the involvement of diffusible radicals and proton-equilibriums, explaining analogous outcomes in mOxPhos chemistry. Further, we demonstrate that superoxide (diffusible reactive oxygen species, DROS) enables in vitro ATP synthesis from ADP+phosphate, and show that this reaction is inhibited by CN. Therefore, practically instantaneous CN ion-radical interactions with DROS in matrix catalytically disrupt mOxPhos, explaining the acute lethal effect of CN.
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http://dx.doi.org/10.1515/bmc-2020-0004DOI Listing
March 2020

Acute toxicity of cyanide in aerobic respiration: Theoretical and experimental support for murburn explanation.

Biomol Concepts 2020 03 17;11(1):32-56. Epub 2020 Mar 17.

Department of Biosciences and Bioengineering, Indian Institute of Technology Guwahati, Guwahati, Assam, India-781039.

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http://dx.doi.org/10.1515/bmc-2020-0004DOI Listing
March 2020

Chemiosmotic and murburn explanations for aerobic respiration: Predictive capabilities, structure-function correlations and chemico-physical logic.

Arch Biochem Biophys 2019 11 14;676:108128. Epub 2019 Oct 14.

Institute of Chemical Kinetics and Combustion, Russian Academy of Sciences, St. Institutskaya 3, 630090, Novosibirsk, Russia. Electronic address:

Since mid-1970s, the proton-centric proposal of 'chemiosmosis' became the acclaimed explanation for aerobic respiration. Recently, significant theoretical and experimental evidence were presented for an oxygen-centric 'murburn' mechanism of mitochondrial ATP-synthesis. Herein, we compare the predictive capabilities of the two models with respect to the available information on mitochondrial reaction chemistry and the membrane proteins' structure-function correlations. Next, fundamental queries are addressed on thermodynamics of mitochondrial oxidative phosphorylation (mOxPhos): (1) Can the energy of oxygen reduction be utilized for proton transport? (2) Is the trans-membrane proton differential harness-able as a potential energy capable of doing useful work? and (3) Whether the movement of miniscule amounts of mitochondrial protons could give rise to a potential of ~200 mV and if such an electrical energy could sponsor ATP-synthesis. Further, we explore critically if rotary ATPsynthase activity of Complex V can account for physiological ATP-turnovers. We also answer the question- "What is the role of protons in the oxygen-centric murburn scheme of aerobic respiration?" Finally, it is demonstrated that the murburn reaction model explains the fast kinetics, non-integral stoichiometry and high yield of mOxPhos. Strategies are charted to further demarcate the two explanations' relevance in the cellular physiology of aerobic respiration.
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http://dx.doi.org/10.1016/j.abb.2019.108128DOI Listing
November 2019

Aerobic respiration: proof of concept for the oxygen-centric murburn perspective.

J Biomol Struct Dyn 2019 10 8;37(17):4542-4556. Epub 2019 Jan 8.

Department of Biotechnology, Indian Institute of Technology Guwahati , Guwahati , Assam, India.

The inner mitochondrial membrane protein complexes (I-V) and prokaryotic respiratory machinery are examined for a deeper understanding of their structure-function correlations and dynamics. analysis of the structure of complexes I-IV, docking studies and erstwhile literature confirm that they carry sites which are in close proximity to DROS (diffusible reactive oxygen species) generating redox centers. These findings provide supportive evidence for the newly proposed oxygen-centric chemical-coupling mechanism (murburn concept), wherein DROS catalyzes the esterification of inorganic phosphate to ADP. Further, in a reductionist system, we demonstrate that a DROS (like superoxide) can effectively esterify inorganic phosphate to ADP. The impact of these findings and the interactive dynamics of classical inhibitors (rotenone and cyanide), uncouplers (dinitrophenol and uncoupling protein) and other toxins (atractyloside and oligomycin) are briefly discussed. • Earlier perception: Complexes (I-IV) pump protons and Complex V make ATP (aided by protons) • Herein: Respiratory molecular machinery is probed for new structure-function correlations • Analyses: Quantitative arguments discount proton-centric ATP synthesis in mitochondria and bacteria • data: ADP-binding sites and O/ diffusible reactive oxygen species (DROS)-accessible channels are unveiled in respiratory proteins • data: Using luminometry, ATP synthesis is demonstrated from ADP, Pi and superoxide • Inference: Findings agree with decentralized ADP-Pi activation via oxygen-centric murburn scheme Communicated by Ramaswamy H. Sarma.
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http://dx.doi.org/10.1080/07391102.2018.1552896DOI Listing
October 2019
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