Molecular Modelling of the Active Site of Enkephalin‐Degrading Neutral Endopeptidase‐24.11 (Enkephalinase) An Active Site Model for Neutral Endopeptidase‐24.11
作者:
Peter R. Andrews,
Magdy N. Iskander,
John Issa,
James A. Reiss,
期刊:
Quantitative Structure‐Activity Relationships
(WILEY Available online 1988)
卷期:
Volume 7,
issue 1
页码: 1-6
ISSN:0931-8771
年代: 1988
DOI:10.1002/qsar.19880070102
出版商: WILEY‐VCH Verlag
关键词: Enkephalinase;neutral endopeptidase‐24.11;thermolysin;angiotensin‐converting enzyme;carboxypeptidase A;phosphoramidon;active site comparison;peptidase speceficity;conformational analysis;computer graphics
数据来源: WILEY
摘要:
AbstractThe active site regions of thermolysin (TLN) and carboxypeptidase A (CPA) are directly compared by superimposition of the published crystal structures of eight TLN/inhibitor complexes and four CPA‐inhibitor complexes. There is a remarkable similarity in the S′1region of these two zinc metalloenzymes, and it is suggested that this may be a common feature among other enzymes of this class, including the enkephalin‐degrading neutral endopeptidase or “enkephalinase” (NEP‐24.11). Assuming this common feature, the possible geometry of the S′2region of enkephalinase was determined by performing classical potential energy calculations on potent NEP‐24.11 inhibitors. The active conformation of these inhibitors was thus identified as similar to that found in the X‐ray crystal structure of TLN/inhibitor complexes. It is proposed that the active site region of TLN should serve as a reasonable model for that of NEP‐24.11. Extension of the model to the case of angiotensin‐converting enzyme (ACE) showed that this enzyme might have a similar S′1region to the other three enzymes, and allowed further definition of the ACE model previously deve
点击下载:
PDF
(631KB)
返 回