Structural basis for the acyl chain selectivity and mechanism of UDP-N-acetylglucosamine acyltransferase
Structural basis for the acyl chain selectivity and mechanism of UDP-N-acetylglucosamine acyltransferase
复制标题
DOI：
10.1073/pnas.0705833104
复制
发表时间：
2007-08-21
影响因子：
11.1
通讯作者：
Raetz, Christian R. H.
中科院分区：
文献类型：
--
作者：
Williams, Allison H.;Raetz, Christian R. H.
UDP-N-乙酰葡糖胺（UDP-GlcNAc）酰基转移酶（LpxA）催化脂质A生物合成的第一步，即R-3-羟酰基链从R-3-羟酰基酰基载体蛋白可逆转移至UDP-GlcNAc的葡糖胺3-OH基团。大肠杆菌LpxA对R-3-羟基肉豆蔻酸具有高度选择性。对E.大肠杆菌LpxA同源三聚体，确定以前在脂质底物或产品的情况下，揭示了LpxA包含一个不寻常的，左手平行的P-螺旋折叠。我们已经解决了E. coliLpxA与结合产物UDP-3-O-（R-3-羟基肉豆蔻酰基）-GicNAc的分离度为1.74埃，与结合产物UDP-3-O-（R-3-羟基癸酰基）GlcNAc的分离度为1.85埃。这些复合物的结构是一致的诱变推断的催化机制，并与最近的3.0埃结构的LpxA与绑定UDP-GlcNAc。我们的结构显示了LpxA如何选择14-碳R-3-羟基酰基链，并揭示了UDP结合的两种模式。
UDP-N-acetylglucosamine (UDP-GlcNAc) acyltransferase (LpxA) catalyzes the first step of lipid A biosynthesis, the reversible transfer of the R-3-hydroxyacyl chain from R-3-hydroxyacyl acyl carrier protein to the glucosamine 3-OH group of UDP-GlcNAc. Escherichia coli LpxA is highly selective for R-3-hydroxymyristate. The crystal structure of the E. coli LpxA homotrimer, determined previously in the absence of lipid substrates or products, revealed that LpxA contains an unusual, left-handed parallel P-helix fold. We have now solved the crystal structures of E. coli LpxA with the bound product UDP-3-O-(R-3-hydroxymyristoyl)-GicNAc at a resolution of 1.74 angstrom and with bound UDP-3-O-(R-3-hydroxydecanoyl)GlcNAc at 1.85 angstrom. The structures of these complexes are consistent with the catalytic mechanism deduced by mutagenesis and with a recent 3.0-angstrom structure of LpxA with bound UDP-GlcNAc. Our structures show how LpxA selects for 14-carbon R-3-hydroxyacyl chains and reveal two modes of UDP binding.