Structure of the hexapeptide xenobiotic acetyltransferase from Pseudomonas aeruginosa
Structure of the hexapeptide xenobiotic acetyltransferase from Pseudomonas aeruginosa
复制标题
DOI：
10.1021/bi980106v
复制
发表时间：
1998-05-12
期刊：
影响因子：
2.9
通讯作者：
Roderick, SL
中科院分区：
文献类型：
--
作者：
Beaman, TW;Sugantino, M;Roderick, SL
来自铜绿假单胞菌PA103的外生乙酰转移酶（PaXAT）的晶体结构已经确定，以及它与底物氯霉素和辅助因子类似物脱硫辅酶A的配合物，PaXAT是大六肽酰基转移酶家族的一员，该家族的酶显示6个残基六肽重复序列基序的串联重复拷贝，编码左旋平行β螺旋（L β H）结构域。外生乙酰转移酶是一类六肽酰基转移酶，由微生物酶组成，利用乙酰辅酶a酰基化各种羟基受体。三聚体PaXAT的活性位点是一个短通道，氯霉素和辅酶类似物脱硫辅酶a分别从两端射入。该隧道由两个独立的L - β - H结构域的平坦平行β片和一个扩展的39个残基环组成。延伸环的His 79从咪唑NE2原子到氯霉素的3-羟基，从ND1基团到Thr 86的肽氧形成氢键，该组氨酸残基的相互作用与结构无关的III型氯霉素乙酰转移酶的相互作用相似，表明PaXAT的His 79可能具有相似的定位和互变异构稳定性，可作为一般碱催化剂。
The crystal structure of the xenobiotic acetyltransferase from Pseudomonas aeruginosa PA103 (PaXAT) has been determined, as well as that of its complex with the substrate chloramphenicol and the cofactor analogue desulfo-coenzyme A, PaXAT is a member of the large hexapeptide acyltransferase family of enzymes that display tandem repeated copies of a six-residue hexapeptide repeat sequence motif encoding a left-handed parallel beta helix (L beta H) structural domain. The xenobiotic acetyltransferase class of hexapeptide acyltransferases is composed of microbial enzymes that utilize acetyl-CoA to acylate a variety of hydroxyl-bearing accepters. The active site of trimeric PaXAT is a short tunnel into which chloramphenicol and the cofactor analogue desulfo-CoA project from opposite ends. This tunnel is formed by the flat parallel beta sheets of two separate L beta H domains and an extended 39-residue loop. His 79 of the extended loop forms hydrogen bonds from its imidazole NE2 atom to the 3-hydroxyl group of chloramphenicol and from its ND1 group to the peptide oxygen of Thr 86, The interactions of this histidine residue are similar to those found in the structurally unrelated type III chloramphenicol acetyltransferase and suggest that His 79 of PaXAT maybe similarly positioned and tautomerically stabilized to serve as a general base catalyst.