Function of Laccases in Anopheles gambiae

冈比亚按蚊漆酶的功能

• 批准号: 7635843
• 负责人: Michael R Kanost
• 金额: $ 37.97万
• 依托单位: KANSAS STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-07-01 至 2011-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7635843
• 关键词: Active Sites; Aedes; Affect; Africa; Anopheles Genus; Anopheles gambiae; Apis; Bacteria; Biochemical; Biology; Blood; Bombyx mori; Catechols; Cell Wall; Characteristics; Chemicals; Chorion; Copper; Culicidae; Data; Development; Diet; Disease; Docking; Drosophila melanogaster; Drug Metabolic Detoxication; Egg Shell; Environment; Enzymes; Exposure to; Genes; Genome; Goals; Health; Homeostasis; Human; In Situ Hybridization; Insecta; Insecticides; Invertebrates; Investigation; Iron; Kinetics; Knowledge; Laccase; Lead; Libraries; Lignin; Malaria; Manduca sexta; Messenger RNA; Molecular; Morphogenesis; Mosquito Control; Organism; Orthologous Gene; Oxidases; Pattern; Physiological; Physiological Processes; Physiology; Pigmentation physiologic function; Pigments; Poison; Population; Process; RNA Interference; Reaction; Recombinants; Research; Research Personnel; Role; Skin tanning; Staging; Structure-Activity Relationship; Substrate Interaction; Substrate Specificity; Testing; Tribolium; Vertebrates; Virulence; Work; Wound Healing; analog; base; design; disease transmission; feeding; fungus; human disease; inhibitor/antagonist; iron metabolism; metal metabolism; metal poisoning; mortality; plant fungi; research study; vector

DESCRIPTION (provided by applicant): Project summary: Laccases are copper-containing oxidases with broad substrate specificity. They have been implicated in a variety of physiological processes in plants and fungi, including lignin synthesis and degradation, morphogenesis, pigmentation, detoxification, and virulence. Related multicopper oxidases are involved in protection against metal toxicity in bacteria and fungi. Whether laccases have similar functions in insects is unknown, as laccases have not previously been investigated in insects in detail. The one identified role of insect laccases is in catalyzing cuticle tanning and sclerotization reactions, but preliminary results suggest that some insect laccase genes may have other functions. The long term goals of this research are to determine the function of six putative laccases in the mosquito, Anopheles garnbiae, to increase our understanding of laccase-substrate interactions, and eventually to use this information to develop strategies to reduce disease transmission by mosquitoes. This project has three specific aims designed to test hypotheses regarding potential functions for laccases in mosquito physiology and to investigate laccase inhibitors for use in biochemical analyses of laccase function and for testing whether laccases may be a potentially useful new target for chemical control of mosquitoes. 1) Investigate the role of laccases in cuticle sclerotization, pigmentation, wound healing, and egg shell tanning. 2) Determine whether laccases have a role in protecting insects from toxic substances such as phenolic compounds in the larval environment or iron in the blood meal. 3) Design, synthesize, and test inhibitors of Anopheles laccases for exploring the laccase active site and for tests of the inhibitors' effects on mosquito development and survival. Relevance: Because they are vectors of human diseases, mosquitoes have a tremendous human health impact, and Anopheles gambiae is particularly important as the major vector of malaria in Africa. Studies of mosquito laccases will increase our understanding of fundamental processes in mosquito biology and may provide knowledge regarding how these insects transmit diseases or how they tolerate toxic chemicals. Disrupting laccase function may provide a new mechanism for controlling mosquito populations.

描述（由申请人提供）：项目摘要：腔酶是具有广泛底物特异性的含铜的氧化酶。它们与植物和真菌的各种生理过程有关，包括木质素合成和降解，形态发生，色素沉着，排毒和毒力。相关的多载氧化酶涉及细菌和真菌中金属毒性的保护。 laccases在昆虫中是否具有相似的功能是未知的，因为以前尚未详细研究laccases。昆虫钩酶的一种确定的作用是在催化角质层晒黑和硬化反应中，但初步结果表明，某些昆虫漆酶基因可能具有其他功能。这项研究的长期目标是确定蚊子中六个假定的lac酶的功能，即Anopheles garnbiae，以增强我们对漆酶 - 基底相互作用的理解，并最终使用这些信息来制定策略来减少蚊子通过蚊子传播的策略。该项目具有三个特定的目的，旨在测试有关蚊子生理学漆酶潜在功能的假设，并研究用于漆酶功能的生化分析的漆酶抑制剂，并测试laccase是否可能是蚊子化学控制的潜在有用的新目标。 1）研究lac酶在表皮硬化，色素沉着，伤口愈合和蛋壳晒黑中的作用。 2）确定laccases在保护昆虫免受幼虫环境中的酚类化合物等有毒物质或血液中铁的作用。 3）设计，合成和测试肛门漆酶的抑制剂，用于探索漆酶的活性位点，并测试抑制剂对蚊子发育和生存的影响。相关性：由于它们是人类疾病的向量，因此蚊子具有巨大的人类健康影响，而Anopheles Gambiae尤其重要，因为它们是非洲疟疾的主要媒介。蚊子灌木丛的研究将增加我们对蚊子生物学基本过程的理解，并可能提供有关这些昆虫如何传播疾病或如何耐受毒性化学物质的知识。破坏漆箱功能可以提供控制蚊子种群的新机制。