Dihydroorotase

Function

Dihydroorotase (DHO) catalyzes the reversible interconversion of carbamoyl aspartate to dihydroorotate in the pyrimidine biosynthesis pathway^[1].

Relevance

The difference between bacterial and mammalian DHO makes it a promising drug target^[2].

Structural highlights

The 3D structure of the complex of DHO with dihydroorotate and carbamoyl aspartate shows these contacts includes electrostatic interactions. Water molecules are shown as red spheres. The substrate ^[3].

3D structures of dihydroorotase

Dihydroorotase 3D structures

Dihydroorotate with ubunit A in deep sky blue and subunit B in green, complex with dihydroorotate, carbamoyl aspartate and Zn+2 ions (PDB ID 2z24)

Drag the structure with the mouse to rotate

ReferencesReferences

↑ Porter TN, Li Y, Raushel FM. Mechanism of the dihydroorotase reaction. Biochemistry. 2004 Dec 28;43(51):16285-92. doi: 10.1021/bi048308g. PMID:15610022 doi:http://dx.doi.org/10.1021/bi048308g
↑ Lipowska J, Miks CD, Kwon K, Shuvalova L, Zheng H, Lewinski K, Cooper DR, Shabalin IG, Minor W. Pyrimidine biosynthesis in pathogens - Structures and analysis of dihydroorotases from Yersinia pestis and Vibrio cholerae. Int J Biol Macromol. 2019 Sep 1;136:1176-1187. doi:, 10.1016/j.ijbiomac.2019.05.149. Epub 2019 Jun 15. PMID:31207330 doi:http://dx.doi.org/10.1016/j.ijbiomac.2019.05.149
↑ Lee M, Maher MJ, Christopherson RI, Guss JM. Kinetic and structural analysis of mutant Escherichia coli dihydroorotases: a flexible loop stabilizes the transition state. Biochemistry. 2007 Sep 18;46(37):10538-50. Epub 2007 Aug 21. PMID:17711307 doi:10.1021/bi701098e

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

Michal Harel, Alexander Berchansky

[1] Porter TN, Li Y, Raushel FM. Mechanism of the dihydroorotase reaction. Biochemistry. 2004 Dec 28;43(51):16285-92. doi: 10.1021/bi048308g. PMID:15610022 doi:http://dx.doi.org/10.1021/bi048308g

[2] Lipowska J, Miks CD, Kwon K, Shuvalova L, Zheng H, Lewinski K, Cooper DR, Shabalin IG, Minor W. Pyrimidine biosynthesis in pathogens - Structures and analysis of dihydroorotases from Yersinia pestis and Vibrio cholerae. Int J Biol Macromol. 2019 Sep 1;136:1176-1187. doi:, 10.1016/j.ijbiomac.2019.05.149. Epub 2019 Jun 15. PMID:31207330 doi:http://dx.doi.org/10.1016/j.ijbiomac.2019.05.149

[3] Lee M, Maher MJ, Christopherson RI, Guss JM. Kinetic and structural analysis of mutant Escherichia coli dihydroorotases: a flexible loop stabilizes the transition state. Biochemistry. 2007 Sep 18;46(37):10538-50. Epub 2007 Aug 21. PMID:17711307 doi:10.1021/bi701098e

[1]

[2]

[3]