Ca-asp bound X-ray structure and inhibition of Bacillus anthracis dihydroorotase (DHOase).

ABSTRACT: Dihydroorotase (DHOase) is the third enzyme in the de novo pyrimidine synthesis pathway and is responsible for the reversible cyclization of carbamyl-aspartate (Ca-asp) to dihydroorotate (DHO). DHOase is further divided into two classes based on several structural characteristics, one of which is the length of the flexible catalytic loop that interacts with the substrate, Ca-asp, regulating the enzyme activity. Here, we present the crystal structure of Class I Bacillus anthracis DHOase with Ca-asp in the active site, which shows the peptide backbone of glycine in the shorter loop forming the necessary hydrogen bonds with the substrate, in place of the two threonines found in Class II DHOases. Despite the differences in the catalytic loop, the structure confirms that the key interactions be

SUBMITTER: Rice AJ 

PROVIDER: S-EPMC5045712 | biostudies-literature | 2016 Oct

REPOSITORIES: biostudies-literature