Structure-function analysis of Burkholderia phymatum 3-dehydroquinate dehydratase (BpDHQase)

Abstract

The Seattle Structural Genomics Center for Infectious Diseases (SSGCID) has determined the structures of proteins from different Burkholderia because they cause diseases and are agents for biological warfare. The current project is a collaboration with the SSGCID. Identifying new drug targets for Burkholderia species includes examining the potential effects on beneficial members like B. phymatum. B. phymatum is a nitrogen-fixing symbiote of the mimosa legume species. This project investigates the structure and function of 3-dehydroquinate dehydratase (DHQase) from B. phymatum. DHQase catalyzes the third step of the shikimate pathway, the interconversion of 3-dehydroquinate and 3- dehydroshikimate. This step is vital for the proper synthesis of phenylalanine, tryptophan, tyrosine, and other aromatic metabolites. The shikimate pathway is absent in mammals and DHQases and other enzymes in the pathway have been investigated as drug targets for multiple bacterial species. Here we present the structure-function analysis of Burkholderia phymatum 3-dehydroquinate dehydratase (BpDHQase). Our reveal that BpDHQase is a catalytically active and has structural features that are typical of bacterial type II DHQases.