CRABPs Alter all-trans-Retinoic Acid Metabolism by CYP26A1 via Protein-Protein Interactions.

ABSTRACT: Cellular retinoic acid binding proteins (CRABP1 and CRABP2) bind all-trans-retinoic acid (atRA), the active metabolite of vitamin A, with high affinity. CRABP1 and CRABP2 have been shown to interact with the atRA-clearing cytochrome P450 enzymes CYP26B1 and CYP26C1 and with nuclear retinoic acid receptors (RARs). We hypothesized that CRABP1 and CRABP2 also alter atRA metabolism and clearance by CYP26A1, the third key atRA-metabolizing enzyme in the CYP26 family. Based on stopped-flow experiments, atRA bound CRABP1 and CRABP2 with K_d values of 4.7 nM and 7.6 nM, respectively. The unbound atRA K_m values for 4-OH-atRA formation by CYP26A1 were 4.7 ± 0.8 nM with atRA, 6.8 ± 1.7 nM with holo-CRABP1 and 6.1 ± 2.

SUBMITTER: Yabut KCB 

PROVIDER: S-EPMC9105409 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature