Carbonyl reductase 1 (CBR1), a short-chain dehydrogenase/reductase, is important in the phase I reduction of drugs. Glutathione (GSH) facilitates the access of low-affinity substrates to the CBR1 active site. This study investigates the path of substrates to the CBR1 active site when GSH occludes the entrance to NADP and binds its catalytic residues. A set of CBR1 structures bound with GSH were subjected to comprehensive docking and molecular dynamics (MD) simulations. The glycine moiety of GSH dangled within the active site, converting the active site into ON/OFF status, while the glutamate residue slips into a hydrophobic cavity, allowing more room for driving the substrate toward the active residues. GSH spontaneously moves within the apoCBR1 binding site and acts as an internal control barrier that selects substrates entering the catalytic site. The VAL230-TYR251 was most flexible in ApoCBR1 structure and showed a lower degree of flexibility upon the binding of inhibitors.

羰基还原酶1（CBR1）是一种短链脱氢酶/还原酶，在药物的I期还原中很重要。谷胱甘肽（GSH）促进低亲和力底物进入CBR1活性位点。这项研究调查了当GSH堵塞NADP的入口并结合其催化残基时底物到达CBR1活性位点的途径。一组与GSH结合的CBR1结构进行了全面的对接和分子动力学（MD）模拟。GSH的甘氨酸部分在活性位点内晃动，将活性位点转换为ON / OFF状态，而谷氨酸残基滑入疏水腔中，为驱动底物向活性残基提供了更多空间。GSH自发地在apoCBR1结合位点内移动，并作为内部控制屏障，选择进入催化位点的底物。VAL230-TYR251在ApoCBR1结构中最灵活，在结合抑制剂后显示出较低的柔韧性。