8ELM

Apo human biliverdin reductase beta (293K)

Summary for 8ELM

• Entry DOI: 10.2210/pdb8elm/pdb
• Descriptor: Flavin reductase (NADPH), SODIUM ION (3 entities in total)
• Functional Keywords: apo, room-temperature, oxidoreductase
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 1
• Total formula weight: 22171.34

Authors

McLeod, M.J.,Eisenmesser, E.Z.,Lee, E.,Thorne, R.E. (deposition date: 2022-09-26, release date: 2023-09-06, Last modification date: 2023-09-13)

Primary citation

Lee, E.,McLeod, M.J.,Redzic, J.S.,Marcolin, B.,Thorne, R.E.,Agarwal, P.,Eisenmesser, E.Z.
Identifying structural and dynamic changes during the Biliverdin Reductase B catalytic cycle.
Front Mol Biosci, 10:1244587-1244587, 2023

PubMed Abstract: Biliverdin Reductase B (BLVRB) is an NADPH-dependent reductase that catalyzes the reduction of multiple substrates and is therefore considered a critical cellular redox regulator. In this study, we sought to address whether both structural and dynamics changes occur between different intermediates of the catalytic cycle and whether these were relegated to just the active site or the entirety of the enzyme. Through X-ray crystallography, we determined the apo BLVRB structure for the first time, revealing subtle global changes compared to the holo structure and identifying the loss of a critical hydrogen bond that "clamps" the R78-loop over the coenzyme. Amide and Cα chemical shift perturbations were used to identify environmental and secondary structural changes between intermediates, with more distant global changes observed upon coenzyme binding compared to substrate interactions. NMR relaxation rate measurements provided insights into the dynamic behavior of BLVRB during the catalytic cycle. Specifically, the inherently dynamic R78-loop that becomes ordered upon coenzyme binding persists through the catalytic cycle while similar regions experience dynamic exchange. However, the dynamic exchange processes were found to differ through the catalytic cycle with several groups of residues exhibiting similar dynamic responses. Finally, both local and distal structural and dynamic changes occur within BLVRB that are dependent solely on the oxidative state of the coenzyme. Thus, through a comprehensive analysis here, this study revealed structural and dynamic alterations in BLVRB through its catalytic cycle that are not simply relegated to the active site, but instead, are allosterically coupled throughout the enzyme.

PubMed: 37645217
DOI: 10.3389/fmolb.2023.1244587

Experimental method

X-RAY DIFFRACTION (2.19 Å)