6CTY

Crystal structure of dihydroorotase pyrC from Yersinia pestis in complex with zinc and malate at 2.4 A resolution

Replaces:  5V0G

Summary for 6CTY

• Entry DOI: 10.2210/pdb6cty/pdb
• Descriptor: Dihydroorotase, ZINC ION, D-MALATE, ... (4 entities in total)
• Functional Keywords: structural genomics, dihydroorotase, zinc, csgid, center for structural genomics of infectious diseases, hydrolase
• Biological source: Yersinia pestis
• Total number of polymer chains: 6
• Total formula weight: 249886.33

Authors

Lipowska, J.,Shabalin, I.G.,Winsor, J.,Woinska, M.,Cooper, D.R.,Kwon, K.,Shuvalova, L.,Anderson, W.F.,Minor, W.,Center for Structural Genomics of Infectious Diseases (CSGID) (deposition date: 2018-03-23, release date: 2018-04-04, Last modification date: 2023-11-15)

Primary citation

Lipowska, J.,Miks, C.D.,Kwon, K.,Shuvalova, L.,Zheng, H.,Lewinski, K.,Cooper, D.R.,Shabalin, I.G.,Minor, W.
Pyrimidine biosynthesis in pathogens - Structures and analysis of dihydroorotases from Yersinia pestis and Vibrio cholerae.
Int.J.Biol.Macromol., 136:1176-1187, 2019

PubMed Abstract: The de novo pyrimidine biosynthesis pathway is essential for the proliferation of many pathogens. One of the pathway enzymes, dihydroorotase (DHO), catalyzes the reversible interconversion of N-carbamoyl-l-aspartate to 4,5-dihydroorotate. The substantial difference between bacterial and mammalian DHOs makes it a promising drug target for disrupting bacterial growth and thus an important candidate to evaluate as a response to antimicrobial resistance on a molecular level. Here, we present two novel three-dimensional structures of DHOs from Yersinia pestis (YpDHO), the plague-causing pathogen, and Vibrio cholerae (VcDHO), the causative agent of cholera. The evaluations of these two structures led to an analysis of all available DHO structures and their classification into known DHO types. Comparison of all the DHO active sites containing ligands that are listed in DrugBank was facilitated by a new interactive, structure-comparison and presentation platform. In addition, we examined the genetic context of characterized DHOs, which revealed characteristic patterns for different types of DHOs. We also generated a homology model for DHO from Plasmodium falciparum.

PubMed: 31207330
DOI: 10.1016/j.ijbiomac.2019.05.149

Experimental method

X-RAY DIFFRACTION (2.41 Å)