INSECT DIURETIC HORMONES--STRUCTURES AND FUNCTION

昆虫有低压循环系统，需要利尿剂。 控制马氏管产生尿液的激素。我们 年首次鉴定出昆虫利尿激素(DH)--六叶虫 1989年。现在，在这个不断壮大的卫生署家庭中，有10名成员(4名 与之前的资金确认)，这些在结构上与 促肾上腺皮质激素释放因子/苏维林/尾加压素I家族多肽。 CRF样水解酶的序列的一个非常新颖的方面是它们 具有30-46个残基的氨基末端一半的同源区 序列和分子羧基末端的同源性，但缺口 在大多数序列的中间都是必需的，以便两者都能很好地比对 终极迷你。序列中的这些差距应该会导致 相关昆虫DHS的三维构象；奇怪的是， 除三个已知的CRF样脱氢酶外，所有已知的类似CRF的脱氢酶都激活了 曼杜卡六种。我们提出了分离和鉴定类CRF水解酶的研究。 来自查格斯氏病的媒介--罗德尼线虫和另外两种昆虫 物种。我们计划与Prolixus合作开展关于R.prolixus的工作 多伦多大学的伊恩·奥查德教授，因为拥有这种疾病媒介是 在美国受到严格控制。 我们还将研究成员的相对三维构象 通过计算机建模和物理化学方法， 希望包括X射线结晶学。我们也希望了解更多 六分枝杆菌和水解酶以及其他水解酶是如何与它们的受体相互作用的。 我们建议确定分子的哪个部分确切地激活了 受体，并确定受体分子六分枝杆菌的哪一部分 卫生署是有约束力的。 对这一独特的神经肽家族的研究将提供信息 这在设计具有水解酶活性的小分子方面可能是有用的， 对控制吸血昆虫有很大的潜在用途。类似物 昆虫保幼激素(倍半萜)目前正在商业化 用作极其安全、特定的昆虫防治剂。

Insects have low pressure circulatory systems and require diuretic hormones to control production of urine by Malpighian tubules. We identified the first insect diuretic hormone (DH), Manduca sexta DH, in 1989. There are now ten members of this growing family of DH (four identified with prior funding), which are structurally homologous to the corticotropin releasing factor/sauvagine/urotensin I family of peptides. An extremely novel aspect of the sequences of the CRF-like DH is that they have homologous regions for the amino terminal half of the 30-46 residue sequence, and homology at the carboxyl terminus of the molecule but gaps are required in the middle of most sequences for good alignment of both termini. These gaps in the sequence should cause profound differences in the three dimensional conformation of the related insect DHs; curiously, all but three of the known CRF-like DH activate Malpighian tubules of Manduca sexta. We propose studies to isolate and identify CRF-like DH from Rhodnius prolixus, a vector of Chagas' disease, and two other insect species. We plan to do the work on R. prolixus in collaboration with Prof. Ian Orchard, U. of Toronto, as possession of this disease vector is strictly controlled in the US. We will also study the relative three dimensional conformation of members of this family of DH by computer modeling and by physico-chemical methods, hopefully including X-ray crystallography. We also hope to learn more about how M. sexta and DH, and other DH, interact with their receptors. We propose to determine exactly what part of the molecule activates the receptor, and to determine to what part of the receptor molecule M. sexta DH binds. Studies on this unique family of neuropeptides will provide information which may be of utility in designing small molecules with DH activity, potentially of great use for control of blood-sucking insects. Analogues of insect juvenile hormones (sesquiterpenoids) are currently in commercial use as extremely safe, specific insect control agents.