Chai C. Gopalasingam

ORCID: 0000-0002-9014-9380
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About
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Research Areas
  • Photosynthetic Processes and Mechanisms
  • ATP Synthase and ATPases Research
  • Enzyme Structure and Function
  • Porphyrin and Phthalocyanine Chemistry
  • Microbial metabolism and enzyme function
  • Metal-Catalyzed Oxygenation Mechanisms
  • Mass Spectrometry Techniques and Applications
  • Advanced Electron Microscopy Techniques and Applications
  • Bacterial Genetics and Biotechnology
  • RNA and protein synthesis mechanisms
  • Mitochondrial Function and Pathology
  • Advanced X-ray Imaging Techniques
  • Antibiotic Resistance in Bacteria
  • Nuclear Physics and Applications
  • X-ray Diffraction in Crystallography
  • Electron Spin Resonance Studies
  • Enzyme Catalysis and Immobilization
  • Protein Structure and Dynamics
  • Particle Accelerators and Free-Electron Lasers
  • Ion Transport and Channel Regulation
  • Algal biology and biofuel production
  • Heat shock proteins research
  • Chemical Reactions and Isotopes
  • Coenzyme Q10 studies and effects
  • X-ray Spectroscopy and Fluorescence Analysis

SPring-8
2021-2024

University of Hyogo
2021-2024

University of Liverpool
2019-2022

Health & Life (Taiwan)
2021

University of Birmingham
2019

Institute of Molecular Biology and Biophysics
2017

Significance The short-lived intermediate formed during the reduction of nitric oxide (NO) to nitrous (N 2 O) in denitrification, microbial anaerobic respiration, is a key state for understanding generation mechanism N O, known not only as greenhouse gas but also an ozone-depleting substance on global level. This paper combined state-of-the-art, time-resolved techniques, such flow-flash infrared spectroscopy and X-ray free electron laser-based crystallography, captured P450-type NO reductase...

10.1073/pnas.2101481118 article EN Proceedings of the National Academy of Sciences 2021-05-17

qNORs that catalyze the reduction of nitric oxide to nitrous are dimeric and obtain their protons from cytoplasmic end.

10.1126/sciadv.aax1803 article EN cc-by-nc Science Advances 2019-08-02

Existing drugs often suffer in their effectiveness due to detrimental side effects, low binding affinity or pharmacokinetic problems. This may be overcome by the development of distinct compounds. Here, we exploit rich structural basis drug-bound gastric proton pump develop compounds with strong inhibitory potency, employing a combinatorial approach utilizing deep generative models for de novo drug design organic synthesis and cryo-EM analysis. Candidate that satisfy pharmacophores defined...

10.1038/s42003-023-05334-8 article EN cc-by Communications Biology 2023-09-19

Neisseria meningitidis is carried by nearly a billion humans, causing developmental impairment and over 100 000 deaths year. A quinol-dependent nitric oxide reductase (qNOR) plays critical role in the survival of bacterium human host. X-ray crystallographic analyses qNOR, including that from N. ( Nm qNOR) reported here at 3.15 Å resolution, show monomeric assemblies, despite more active dimeric sample being used for crystallization. Cryo-electron microscopic analysis same chromatographic...

10.1107/s2052252520003656 article EN cc-by IUCrJ 2020-03-20

Abstract Antimicrobial resistance (AMR) is a global health problem. Despite the enormous efforts made in last decade, threats from some species, including drug-resistant Neisseria gonorrhoeae , continue to rise and would become untreatable. The development of antibiotics with different mechanism action seriously required. Here, we identified an allosteric inhibitory site buried inside eukaryotic mitochondrial heme-copper oxidases (HCOs), essential respiratory enzymes for life. steric...

10.1038/s41467-022-34771-y article EN cc-by Nature Communications 2022-12-08

Abstract The leading cause of bacterial meningitis, Neisseria meningitidis, deploys a quinol-dependent nitric oxide reductase ( Nm qNOR), belonging to the heme-copper oxidase superfamily. By detoxifying NO, an antimicrobial gas produced by host’s immune system, qNOR enables pathogen survival within hosts. Here, we determined cryoEM structures less active monomer and highly dimer at resolutions 2.25 1.89 Å, respectively, showing structural elements responsible for effective NO reduction....

10.1101/2024.05.16.593792 preprint EN cc-by-nc-nd bioRxiv (Cold Spring Harbor Laboratory) 2024-05-17

Single particle cryo electron microscopy (cryo-EM) is now the major method for determination of integral membrane protein structure. For success a given project type mimetic used extraction from native cell membrane, purification to homogeneity and finally cryo-grid vitrification crucial. Although small molecule amphiphiles - detergents are most widely mimetic, specific tailoring detergent structure single cryo-EM rare demand effective not satisfied. Here, we compare popular lauryl...

10.1002/cplu.202400242 article EN cc-by-nc ChemPlusChem 2024-06-17

10.1107/s2053273323098145 article EN Acta Crystallographica Section A Foundations and Advances 2023-07-07
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