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褪黑素的生物合成:分辨率为2.5埃的血清素N-乙酰基转移酶结构揭示了一种催化机制。

Melatonin biosynthesis: the structure of serotonin N-acetyltransferase at 2.5 A resolution suggests a catalytic mechanism.

作者信息

Hickman A B, Klein D C, Dyda F

机构信息

Laboratory of Developmental Neurobiology, National Institute of Child Health and Human Development, Bethesda, Maryland 20892, USA.

出版信息

Mol Cell. 1999 Jan;3(1):23-32. doi: 10.1016/s1097-2765(00)80171-9.

DOI:10.1016/s1097-2765(00)80171-9
PMID:10024876
Abstract

Conversion of serotonin to N-acetylserotonin, the precursor of the circadian neurohormone melatonin, is catalyzed by serotonin N-acetyltransferase (AANAT) in a reaction requiring acetyl coenzyme A (AcCoA). AANAT is a globular protein consisting of an eight-stranded beta sheet flanked by five alpha helices; a conserved motif in the center of the beta sheet forms the cofactor binding site. Three polypeptide loops converge above the AcCoA binding site, creating a hydrophobic funnel leading toward the cofactor and serotonin binding sites in the protein interior. Two conserved histidines not found in other NATs are located at the bottom of the funnel in the active site, suggesting a catalytic mechanism for acetylation involving imidazole groups acting as general acid/base catalysts.

摘要

血清素转化为昼夜节律神经激素褪黑素的前体N - 乙酰血清素,是由血清素N - 乙酰转移酶(AANAT)在需要乙酰辅酶A(AcCoA)的反应中催化的。AANAT是一种球状蛋白,由一个八链β折叠片层两侧各有五个α螺旋组成;β折叠片层中心的一个保守基序形成辅因子结合位点。三个多肽环在AcCoA结合位点上方汇聚,形成一个通向蛋白质内部辅因子和血清素结合位点的疏水漏斗。在活性位点的漏斗底部有两个在其他NAT中未发现的保守组氨酸,这表明存在一种涉及咪唑基团作为通用酸/碱催化剂的乙酰化催化机制。

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