TY  - JOUR
AU  - Ritacco, Ida
AU  - Saltalamacchia, Andrea
AU  - Spinello, Angelo
AU  - Ippoliti, Emiliano
AU  - Magistrato, Alessandra
TI  - All-Atom Simulations Disclose How Cytochrome Reductase Reshapes the Substrate Access/Egress Routes of Its Partner CYP450s
JO  - The journal of physical chemistry letters
VL  - 11
IS  - 4
SN  - 1948-7185
CY  - Washington, DC
PB  - ACS
M1  - FZJ-2021-00767
SP  - 1189 - 1193
PY  - 2020
AB  - Cytochromes P450 enzymes (CYP450s) promote the oxidative metabolism of a variety of substrates via the electrons supplied by the cytochrome P450 reductase (CPR) and upon formation of a CPR/CYP450 adduct. In spite of the pivotal regulatory importance of this process, the impact of CPR binding on the functional properties of its partner CYP450 remains elusive. By performing multiple microsecond-long all-atom molecular dynamics simulations of a 520 000-atom model of a CPR/CYP450 adduct embedded in a membrane mimic, we disclose the molecular terms for their interactions, considering the aromatase (HA) enzyme as a proxy of the CYP450 family. Our study strikingly unveils that CPR binding alters HA’s functional motions, bolstering a change in the shape and type of the channels traveled by substrates/products during their access/egress to/from the enzyme’s active site. Our outcomes unprecedentedly contribute to extricate the many entangled facets of the CYP450 metabolon, redrafting its intricate panorama from an atomic-level perspective.
LB  - PUB:(DE-HGF)16
C6  - 31986051
UR  - <Go to ISI:>//WOS:000515424300001
DO  - DOI:10.1021/acs.jpclett.9b03798
UR  - https://juser.fz-juelich.de/record/890178
ER  -