STRUCTURE-FUNCTION DETEMINATION OF THE TYPE III HALOACID DEHALOGENASE (HAD) SUPE

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目及 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 卤酸脱卤酶（HAD）超家族由在其活性位点中共享几个保守序列基序的结构同源的酶组成。大多数HAD成员是磷酸水解酶，并且根据结构域组织可以分为三个亚类。在I类和II类中，移动的“帽”结构域在底物结合后重新定向，使活性位点与本体溶剂封闭。第三类的成员缺乏这种额外的域。它是帽结构域，似乎是负责底物特异性。我的研究重点是了解缺乏帽结构域的第三类酶如何能够识别不同的靶标。PSPTO 2114蛋白是一种功能未知的新蛋白，通过系统发育分析，它似乎处于I类和III类HAD成员之间的十字路口。基于序列同源性，看来蜡状芽孢杆菌膦酰乙醛水解酶（PHN），一个I类HAD成员，是已知的最接近的X射线结构，只有24%的序列同一性。“无帽”似乎共享存在于PHN中的类似二聚化结构域。无盖水龙头的结构将提供线索 关于这个超家族是如何进化的，以及提供对III型HAD成员的底物特异性的了解。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The haloacid dehalogenase (HAD) superfamily is comprised of structurally homologous enzymes that share several conserved sequence motifs in their active site. The majority of HAD members are phosphohydrolases and may be divided into three subclasses depending on domain organization. In classes I and II, a mobile "cap" domain reorients upon substrate binding, closing the active site to bulk solvent. Members of the third class lack this additional domain. It is the cap domain that appears to be responsible for substrate specificity. My research has focused on understanding how this third class of enzymes that lacks the cap domain is able to recognize different targets. Protein PSPTO2114 from Pseudomonas syringae or "capless" is a novel protein with unknown function that by phylogenetic analysis, appears to be at the cross roads between class I and III HAD members. Based on sequence homology, it appears that bacillus cereus phosphonoacetaldehyde hydrolase (PHN), a class I HAD member, is the closest known X-ray structure, with only 24% sequence identity. "Capless" appears to share a similar dimerization domain that is present in PHN. The structure of capless wwill provide clues as to how this superfamily has evolved as well as providing insight to substrate specificity of the type III HAD members.