Crystal structure of rat biliverdin reductase

  title={Crystal structure of rat biliverdin reductase},
  author={Akihiro Kikuchi and Sam-Yong Park and Hideyuki Miyatake and Danyu Sun and Michihiko Sato and Tadashi Yoshida and Yoshitsugu Shiro},
  journal={Nature Structural Biology},
Biliverdin reductase (BVR) is a soluble cytoplasmic enzyme that catalyzes the conversion of biliverdin to bilirubin using NADH or NADPH as electron donor. Bilirubin is a significant biological antioxidant, but it is also neurotoxic and the cause of kernicterus. In this study, we have determined the crystal structure of rat BVR at 1.4 Å resolution. The structure contains two domains: an N-terminal domain characteristic of a dinucleotide binding fold (Rossmann fold) and a C-terminal domain that… 
Crystal structure of a biliverdin IXalpha reductase enzyme-cofactor complex.
A substrate-bound structure of cyanobacterial biliverdin reductase identifies stacked substrates as critical for activity
Unexpectedly, two biliverdin molecules, which are designated the proximal and distal biliverdins, bind with stacked geometry in the active site and support that a conserved Arg185 is essential for the catalysis.
Enzymatic Activity and Thermodynamic Stability of Biliverdin IXβ Reductase Are Maintained by an Active Site Serine.
Experimental and thermodynamic modeling studies are undertaken to provide further insight into the role of the cofactor in substrate accessibility and protein folding properties regulating BLVRB catalytic mechanisms and defines a dynamic model for apoBLVRB extending beyond the crystal structure of the binary BLVRb/NADP+ complex.
Activation of biliverdin-IXalpha reductase by inorganic phosphate and related anions.
Evidence is presented that the apparent peak of activity observed at neutral pH with phosphate buffer and NADH as cofactor is an anion-dependent activation, where inorganic phosphate apparently mimics the role played by the 2'-phosphate of NADPH in stabilizing the interaction between NADH and the enzyme.
Expression, purification and preliminary X-ray crystallographic analysis of cyanobacterial biliverdin reductase.
  • A. Watanabe, K. Hirata, K. Wada
  • Chemistry
    Acta crystallographica. Section F, Structural biology and crystallization communications
  • 2011
The structure of cyanobacterial BVR may provide insights into the mechanisms of its enzymatic and physiological functions.
New insights into biliverdin reductase functions: linking heme metabolism to cell signaling.
These, together with the protein's primary and secondary features, intimately link BVR to the entire spectrum of cell-signaling cascades.
Biliverdin Reductase: More than a Namesake – The Reductase, Its Peptide Fragments, and Biliverdin Regulate Activity of the Three Classes of Protein Kinase C
Small fragments of hBVR are potent activators and inhibitors of the ERK kinases and PKCs: as such, they suggest the potential application of BVR-based technology in therapeutic settings.
Biliverdin reductase in cardiovascular inflammation
It is shown that BVR acts in an anti-inflammatory manner in the endothelium; by increasing eNOS activation and nitric oxide release, inducing HO-1 protein expression and by inhibiting TNFα-induced leukocyte-endothelium interaction.


Crystallization and preliminary X-ray diffraction analysis of a rat biliverdin reductase.
The first crystallization and preliminary crystallographic study of recombinant rat BVR expressed in Escherichia coli and the complete determination of the crystallographic structure is currently in progress using MAD (multiwavelength anomalous diffraction) data from an Ir-derivative crystal.
Human biliverdin IXalpha reductase is a zinc-metalloprotein. Characterization of purified and Escherichia coli expressed enzymes.
The protein produced by an expression plasmid in which the insert was cloned in frame with lacZ sequences was characterized, and demonstrated dual pH and cofactor dependence, but as suggested by kinetic analysis, the human enzyme may also use NADH as cofactor, as opposed to the rat reductase, which most likely utilizes only NADPH under physiological conditions.
Characterization of Cyanobacterial Biliverdin Reductase
Absorbance spectra and high performance liquid chromatography retention times of the reaction product reaction match those of authentic bilirubin, the product of the reduction of biliverdin by the mammalian enzymes, providing the first evidence for the formation of bilirubs in bacteria.
Purification and characterization of biliverdin reductase from rat liver.
Site-directed mutagenesis of cysteine residues in biliverdin reductase. Roles in substrate and cofactor binding.
Analysis by circular dichroism at far-ultraviolet wavelengths suggests that the alterations in activity are not the result of changes in the secondary structure of these mutants, and is consistent with Cys73 having a central role in substrate/cofactor binding while biliverdin reductase can function, albeit at a reduced rate, with only one of the near C-terminus cysteines.
Kinetic properties and regulation of biliverdin reductase.
Purification and properties of biliverdin reductases from pig spleen and rat liver.
Biliverdin reductase was purified from pig spleen soluble fraction to a purity of more than 90% as judged by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and showed properties quite similar to those of the splenic enzyme as regards the biliverdin reducing reaction.
Microsomal heme oxygenase. Characterization of the enzyme.
The kinetics and tissue distribution of the microsomal heme oxygenase suggest that it is of major importance in the physiological degradation of hemoglobin and other hemoproteins to bile pigment.