Determination of the SAG Binding Motif on AgI/II of Streptococcus Mutans

变形链球菌 AgI/II 上 SAG 结合基序的测定

• 批准号: 7484263
• 负责人: Champion Christdoss Selvakumar Deivanayagam
• 金额: $ 35.89万
• 依托单位: UNIVERSITY OF ALABAMA AT BIRMINGHAM
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-09-01 至 2012-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7484263
• 关键词: Address; Adherence; Adhesives; Agglutinins; Alanine; Antigens; Bacteria; Bacterial Adhesins; Bacterial Infections; Binding; Complex; Consensus; Crystallization; Dental Enamel; Dental caries; Development; Drug Design; Environment; Epitopes; Exhibits; Extracellular Matrix; Extracellular Matrix Proteins; Glycoproteins; Goals; Human; I-antigen; Immunoglobulin G; Infection; Invaded; Ions; Lead; Ligand Binding; Maps; Mediating; Membrane Proteins; Metals; Methods; Microbe; Modeling; Modification; Mutation; Nature; Neuraminic Acids; Numbers; Organism; Peptides; Play; Polysaccharides; Process; Proline; Protein Binding; Proteins; Research Personnel; Role; SRCR proteins; Salivary; Secretory Immunoglobulin A; Staphylococcus aureus; Streptococcus adhesin; Streptococcus mutans; Structure; Surface; System; Testing; Tissues; Vaccines; base; extracellular; inhibitor/antagonist; microbial; mutant; novel; programs; scavenger receptor; small molecule

DESCRIPTION (provided by applicant): Bacterial attachment to host tissue is a critical first step in a process that may lead to clinically manifested infections. A bacterial infection can be regarded as a battle between the microbe and the host. This primary campaign starts with the bacteria's attempt to adhere and colonize the host. It is here that the surface components on bacteria play an important role. In Staphyloccocous aureus, the ligand-binding regions of all the surface proteins utilize a conserved DEv-IgG fold to bind to various extracellular matrix molecules through modification of residues and orientation of domains. We hypothesize that every bacterial species has developed its own system of adherence through a definitive adherence-motif. To address this hypothesis, we propose to identify the salivary agglutinin glycoprotein (SAG) adherence motif of Antigen l/ll (Agl/ll), a surface protein adhesin of Streptococcus mutans that is a known etiological agent of dental caries. The means by which Agl/ll interacts with SAG is now known to be mediated through gp340, a glycoprotein that contains scavenger receptor cystein rich (SRCR) domains. To identify the adherence-motif specifically, we will: 1) Determine the crystal structure of the AVP region of Agl/ll; 2) Map and characterize the interaction between the Agl/ll domains and gp340 domains; and finally 3) Create an Agl/ll-gp340 binding model and identify the binding-motif. The identification of the SAG adherence-motif of Agl/ll will facilitate structure-based drug design of either a small molecule or a peptide inhibitor for use in anti-infection therapy or for development of caries vaccine candidates.

描述（由申请人提供）：细菌附着于宿主组织是可能导致临床表现感染的过程中的关键第一步。细菌感染可以被看作是微生物和宿主之间的一场战斗。这一主要活动始于细菌试图粘附并定殖宿主。正是在这里，细菌的表面成分发挥了重要作用。在金黄色葡萄球菌中，所有表面蛋白的配体结合区都利用保守的DEv-IgG折叠，通过残基的修饰和结构域的取向与各种细胞外基质分子结合。我们假设每一种细菌都通过一个确定的粘附基序发展了自己的粘附系统。为了解决这一假设，我们建议确定唾液凝集素糖蛋白（SAG）粘附基序的抗原I/II（Agl/II），表面蛋白粘附变形链球菌，是一个已知的龋齿病原体。现在已知Agl/II与SAG相互作用的方式是通过gp 340介导的，gp 340是一种含有清道夫受体富含半胱氨酸（SRCR）结构域的糖蛋白。为了具体地鉴定粘附基序，我们将：1）确定Agl/II的AVP区域的晶体结构; 2）绘制并表征Agl/II结构域和gp 340结构域之间的相互作用;以及最后3）创建Agl/II-gp 340结合模型并鉴定结合基序。Agl/II的SAG粘附基序的鉴定将促进用于抗感染治疗或用于开发龋齿疫苗候选物的小分子或肽抑制剂的基于结构的药物设计。