文献类型：期刊文献

英文题名：Conformational gating governs ligand recognition in Bacillus subtilis cytochrome P450 CypX

作者：Wang, Yiru[1,2];Li, Ying[1,2]

第一作者：Wang, Yiru

通讯作者：Li, Y[1];Li, Y[2]

机构：[1]Beijing Union Univ, Coll Biochem Engn, Beijing Key Lab Biomass Waste Resource Utilizat, Beijing 100023, Peoples R China;[2]Beijing Union Univ, Coll Biochem Engn, Beijing Key Lab Bioact Subst & Funct Foods, Beijing 100023, Peoples R China

第一机构：北京联合大学生物化学工程学院

通讯机构：[1]corresponding author), Beijing Union Univ, Coll Biochem Engn, Beijing Key Lab Biomass Waste Resource Utilizat, Beijing 100023, Peoples R China;[2]corresponding author), Beijing Union Univ, Coll Biochem Engn, Beijing Key Lab Bioact Subst & Funct Foods, Beijing 100023, Peoples R China.|[1141726]北京联合大学生物化学工程学院;[11417]北京联合大学;[114172]北京联合大学应用文理学院;

年份：2026

外文期刊名：PHYSICAL CHEMISTRY CHEMICAL PHYSICS

收录：;EI(收录号：20261720582756);WOS:【SCI-EXPANDED(收录号:WOS:001747525400001)】；

基金：This work is financially supported by the Project of Cultivation for Young Top-notch Talents of Beijing Municipal Institutions (BPHR202203209).

语种：英文

外文关键词：Bacteria - Bacteriology - Complexation - Conformations - Free energy - Geometry - Hydrogen bonds - Ligands

摘要：Bacterial cytochrome P450s are cornerstone monooxygenases that enable selective oxidation across the fields of metabolism and biocatalysis. Yet, for the orphan Bacillus subtilis enzyme CYP134A1 (CypX), how ligand identity governs conformational readiness remains unclear despite its solved structure. Here we combine atomistic simulations of apo CypX and four ligand-bound complexes with principal-component analysis, two-dimensional free energy surfaces, and an operational three-state classification based on two gating coordinates: dmouth, the distance between the centers of geometry of the BC-loop and FG-loop C alpha sets that reports opening at the channel entrance, and dcover, the distance from the FG-loop C alpha centroid to the heme Fe that reports the cover position over the distal pocket. These descriptors are complemented by reactive-geometry and hydrogen-bond analyses and by MM-PBSA component analysis as a supportive energetic readout. The simulations reveal a conserved mouth-cover landscape with three recurrent basins, open, intermediate, and closed. Ligands mainly redistribute populations across these pre-existing states and reshape gate geometry rather than generating new conformational states. Together, these findings support a conformational-selection mechanism linking ligand recognition, gating, and catalytic readiness in this orphan bacterial P450.