ArticleThe journal of physical chemistry. B2012
Molecular modeling to provide insight into the substrate binding and catalytic mechanism of human biliverdin-IXα reductase.
Article in The journal of physical chemistry. B, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 28 citations in OpenAlex.
- Biliverdinuria Caused by ExonicGenes · 2024Article
- Biliverdin Reductase B Dynamics Are Coupled to Coenzyme Binding.Journal of molecular biology · 2018Article
- Article
- Exploration of binding and inhibition mechanism of a small molecule inhibitor of influenza virus H1N1 hemagglutinin by molecular dynamics simulation.Scientific reports · 2017Article
- A substrate-bound structure of cyanobacterial biliverdin reductase identifies stacked substrates as critical for activity.Nature communications · 2017Article
- Enzymatic Activity and Thermodynamic Stability of Biliverdin IXβ Reductase Are Maintained by an Active Site Serine.Chemistry (Weinheim an der Bergstrasse, Germany) · 2017Article
- Rv2074 is a novel F420 H2 -dependent biliverdin reductase in Mycobacterium tuberculosis.Protein science : a publication of the Protein Society · 2016Article
- Characterization of Aspartate Kinase from Corynebacterium pekinense and the Critical Site of Arg169.International journal of molecular sciences · 2015Article
- Biliverdin reductase isozymes in metabolism.Trends in endocrinology and metabolism: TEM · 2015Review
- Molecular modeling and MM-PBSA free energy analysis of endo-1,4-β-xylanase from Ruminococcus albus 8.International journal of molecular sciences · 2014Article
- Computational study on substrate specificity of a novel cysteine protease 1 precursor from Zea mays.International journal of molecular sciences · 2014Article
- Article
- Stereoselectivity of chalcone isomerase with chalcone derivatives: a computational study.Journal of molecular modeling · 2013Article
- Mesobiliverdin IXα Enhances Rat Pancreatic Islet Yield and Function.Frontiers in pharmacology · 2013Article
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Human biliverdin-IXα reductase (hBVR-A) catalyzes the conversion of biliverdin-IXα to bilirubin-IXα in the last step of heme degradation and is a key enzyme in regulating a wide range of cellular responses. Though the X-ray structure of hBVR-A is available including cofactor, a crystal structure with a bound substrate would be even more useful as a starting point for protein-structure-based inhibitor design, but none have been reported. The present study employed induced fit docking (IFD) to study the substrate binding modes to hBVR-A of biliverdin-IXα and four analogues. The proposed substrate binding modes were examined further by performing molecular dynamics (MD) simulations followed by molecular mechanics Poisson-Boltzmann surface area (MM-PBSA) calculations. The predicted binding free energies for the five biliverdin-IXα analogues match well with the relative potency of their reported experimental binding affinities, supporting that the proposed binding modes are reasonable. Furthermore, the ternary complex structure of hBVR-A binding with biliverdin-IXα and the electron donor cofactor NADPH obtained from MD simulations was exploited to investigate the catalytic mechanism, by calculating the reaction energy profile using the quantum mechanics/molecular mechanics (QM/MM) method. On the basis of our calculations, the energetically preferred pathway consists of an initial protonation of the pyrrolic nitrogen on the biliverdin substrate followed by hydride transfer to yield the reduction product. This conclusion is consistent with a previous mechanistic study on human biliverdin IXβ reductase (hBVR-B).
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.