Structural and functional studies of the metalloendopeptidase (EC 3.4.24.15) involved in degrading gonadotropin releasing hormone.
Structural and functional studies of the metalloendopeptidase (EC 3.4.24.15) involved in degrading gonadotropin releasing hormone.
复制标题
参与降解促性腺激素释放激素的金属内肽酶 (EC 3.4.24.15) 的结构和功能研究。
DOI：
10.1016/s0006-3495(92)81798-8
复制
发表时间：
1992
影响因子：
3.4
通讯作者：
Roberts,JL
中科院分区：
文献类型：
--
作者：
Glucksman,MJ;Orlowski,M;Roberts,JL
Converging biophysical and molecular biological tech-niques including genetic and computer aided engineering are being utilized in the study of zinc-metallo-endopeptidase EC 3.4. 24.15 (EP 24.15), a peptidase involved in the degradation of Gonadotropin releasing hormone (GnRH), the master regulatory decapeptide involved in reproduction. This 71 kDa enzyme rapidly cleaves the Tyr5-Gly6 bond in GnRH, the rate limiting reaction in hormone inactivation. EP 24.15 has been identified and isolated (1, 2) and the full length rat cDNA has recently been sequenced, and used to direct the expression of the functional 645 amino acid protein (3). The sequence of EP 24.15 shows no sequence identity with any known metalloendopeptidases beyond the commonly shared active site motif,-HExxH-, found in this family of enzymes. EP 24.15 is a predominantly cytosolic enzyme that isstable, not glycosylated, and can be modeled with other globular proteins. Hydrophobic Cluster Analysis,(HCA)(4), is a heuristic algorithm ascertaining structural domains by detecting patterns of secondary structure and sequence homology in a two-dimensional analysis. This method has been used to determine if thermolysin may be used in modeling EP 24.15, and extending this analysis to enkephali-nase and angiotensin converting enzyme two other members of the zinc-metalloendopeptidase family. Infor-mation gained from this study would be a step towards modeling substrate and inhibitor interactions to elucidate the conformation of this enzyme, asa probe for the function of this enzyme in vivo, and as a target for pharmacological intervention.
