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

基本信息

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
项目类别：
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

项目摘要

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）：细菌附着在宿主组织上是可能导致临床表现感染的过程中关键的第一步。细菌感染可以被视为微生物与宿主之间的战斗。这一主要活动始于细菌试图粘附和定植宿主。正是在这里，细菌的表面成分发挥着重要作用。在金黄色葡萄球菌中，所有表面蛋白的配体结合区域利用保守的 DEv-IgG 折叠，通过残基修饰和结构域方向结合各种细胞外基质分子。我们假设每个细菌物种都通过明确的粘附基序发展了自己的粘附系统。为了解决这一假设，我们建议鉴定抗原l/ll (Agl/ll)的唾液凝集素糖蛋白(SAG)粘附基序，抗原l/ll是变形链球菌的表面蛋白粘附素，是已知的龋齿病因。现在已知Agl/II与SAG相互作用的方式是通过gp340介导的，gp340是一种含有富含清道夫受体半胱氨酸(SRCR)结构域的糖蛋白。为了具体识别粘附基序，我们将： 1）确定Agl/ll的AVP区域的晶体结构； 2) 绘制并表征 Agl/ll 结构域和 gp340 结构域之间的相互作用；最后 3) 创建 Agl/ll-gp340 结合模型并识别结合基序。 Agl/II 的 SAG 粘附基序的鉴定将有助于基于结构的药物设计，用于抗感染治疗或龋齿疫苗候选物的开发的小分子或肽抑制剂。