X-ray structure of fumarylacetoacetate hydrolase family member Homo sapiens FLJ36880
X-ray structure of fumarylacetoacetate hydrolase family member Homo sapiens FLJ36880
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DOI：
10.1515/bc.2004.122
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发表时间：
2004-10-01
影响因子：
3.7
通讯作者：
Heinemann, U
中科院分区：
文献类型：
--
作者：
Manjasetty, BA;Niesen, FH;Heinemann, U
人蛋白FLJ36880属于富马酰乙酰乙酸水解酶家族。FLJ36880的X射线结构已被确定为2.2分辨率采用蛋白质结构工厂的半自动化高通量结构基因组学方法。FLJ36880采用混合[beta]夹心辊折叠，在晶体和溶液中形成均二聚体。一个Mg[2+]离子通过与三个羧酸氧和三个水分子配位而与二聚体蛋白质的每个亚基结合。这些金属结合位点可从二聚体的相同表面接近，部分原因是十一肽段D29至L39的无序。FLJ36880的整体结构和金属结合位点与来自大肠杆菌C的双功能酶HpcE、来自小家鼠的富马酰乙酰乙酸水解酶和来自大肠杆菌的YcgM（Apc5008）的C末端结构域具有明显的相似性。coli1262。这些相似性为FLJ36880的生化功能和进化关系提供了一个框架。金属结合位点极有可能参与与芳香族氨基酸的催化有关的酶活性。FAH活性位点中的两个点突变（导致人类代谢疾病遗传性酪氨酸血症I型（HTI））影响FLJ36880中结构保守且位于推定催化位点的残基。
The human protein FLJ36880 belongs to the fumarylacetoacetate hydrolase family. The Xray structure of FLJ36880 has been determined to 2.2 a resolution employing the semiautomated highthroughput structural genomics approach of the Protein Structure Factory. FLJ36880 adopts a mixed [beta]sandwich roll fold and forms homodimers in crystals as well as in solution. One Mg[2+] ion is bound to each subunit of the dimeric protein by coordination to three carboxylate oxygens and three water molecules. These metal binding sites are accessible from the same surface of the dimer, partly due to the disorder of the undecapeptide stretch D29 to L39. The overall structure and metal binding site of FLJ36880 bear clear similarities to the Cterminal domain of the bifunctional enzyme HpcE from Escherichia coli C, fumarylacetoacetate hydrolase from Mus musculus and to YcgM (Apc5008) from E. coli 1262. These similarities provide a framework for suggesting biochemical functions and evolutionary relationships of FLJ36880. It appears highly probable that the metal binding sites are involved in an enzymatic activity related to the catabolism of aromatic amino acids. Two point mutations in the activesite of FAH, responsible for the metabolic disease hereditary tyrosinemia type I (HTI) in humans, affect residues that are structurally conserved in FLJ36880 and located in the putative catalytic site.