X-ray crystal structure analysis of phosphoglycerate kinase from gram-negative pathogens: validation of an anti-microbial drug target

因德尔治疗公司不列颠哥伦比亚省的温哥华市中心与阿尔伯塔大学Michael James博士的实验室建立了工业/学术合作关系。 这项合作将调查由Indel的药物靶标识别平台确定的潜在靶标，用于开发新的抗菌药物，以对抗耐药性和医院获得性感染。詹姆斯实验室是使用X射线晶体学技术的结构生物学领域的世界领导者。它将从几种重要的机会性病原体中产生高度纯化的目标酶，以确定目标酶的高分辨率三维结构。结构测定允许筛选化合物文库以鉴定潜在的抑制剂。酶靶点-抑制剂复合物结构的阐明可以验证Indel的预测，并允许对先导抑制剂分子进行结构指导的改进。将通过使用体外酶活性试验测量抑制来监测效价和特异性的增加。 这项合作的社会效益是，这项工作直接解决了耐药性医院获得性细菌感染的可怕问题，以及由此对加拿大医疗保健系统的经济影响。

Indel Therapeutics Inc. of Vancouver, British Columbia has established an industrial/academic collaboration with the laboratory of Dr. Michael James at the University of Alberta. This collaboration will investigate a potential target identified by Indel's drug target identification platform for the development of new antimicrobials to fight drug resistance and hospital acquired infections. The James laboratory is a world leader in the field of structural biology using X-ray crystallographic techniques. It will produce highly purified target enzymes from several important oportunistic pathogens in order to determine the high resolution three dimensional structures of the target enzymes. Structure determination allows screening of compound libraries to identify potential inhibitors. Elucidation of enzyme target-inhibitor complex structures can validate Indel's predictions and allow structure-guided improvements to the lead inhibitor molecules. Increased potency and specificity will be monitored by measuring inhibition using in vitro enzyme activity assays. The societal benefit of this collaboration is that the work directly addresses the dire problem of antibiotic-resistant hospital acquired bacterial infections and the resulting economic impact to the Canadian health care system.