基于机制的5α-还原酶（5AR）活性位点的表征。

Mechanism based representation of the active site of 5 alpha-reductase (5AR).

作者信息

Ahmed S, Denison S

机构信息

School of Applied Chemistry, Kingston University, Kingston upon Thames, Surrey, UK.

出版信息

Bioorg Med Chem Lett. 1998 Sep 22;8(18):2615-70. doi: 10.1016/s0960-894x(98)00463-6.

DOI:10.1016/s0960-894x(98)00463-6

PMID:9873591

Abstract

In the present study, we have attempted to determine a detailed representation of the 5 alpha-Reductase (5AR) active site involving the elucidation of the transition state for the steroid delta 4 reduction reaction (the 'NADPH-substrate' complex), onto which steroidal and non-steroidal inhibitors were superimposed. We conclude that: (i) there is a requirement for groups to mimic the steroid substrate A-ring; (ii) the area about C(3), C(4), C(5) and C(6) of T appears to be sterically hindered, and; (iii) the area of the active site about the C(17) of the steroid substrate does not possess hydrogen bonding groups and is not restricted.

摘要

在本研究中，我们试图确定5α-还原酶（5AR）活性位点的详细表征，其中涉及阐明甾体Δ4还原反应的过渡态（“NADPH-底物”复合物），并将甾体和非甾体抑制剂叠加在该复合物上。我们得出以下结论：（i）需要基团来模拟甾体底物的A环；（ii）T的C（3）、C（4）、C（5）和C（6）周围区域似乎存在空间位阻，并且；（iii）甾体底物C（17）周围的活性位点区域不具有氢键基团且不受限制。