6GDE
DIHYDROOROTASE FROM AQUIFEX AEOLICUS STANDARD (P,T)
Summary for 6GDE
| Entry DOI | 10.2210/pdb6gde/pdb |
| Related | 1XRF 1XRT 3D6N |
| Descriptor | Dihydroorotase, ZINC ION (3 entities in total) |
| Functional Keywords | dihydroorotase, aquifex aeolicus, hydrostatic pressure, room temperature, hydrolase |
| Biological source | Aquifex aeolicus (strain VF5) |
| Total number of polymer chains | 1 |
| Total formula weight | 46692.33 |
| Authors | Prange, T.,Girard, E.,Herve, G.,Evans, D. (deposition date: 2018-04-23, release date: 2019-01-30, Last modification date: 2024-01-17) |
| Primary citation | Prange, T.,Girard, E.,Fourme, R.,Dhaussy, A.C.,Edwards, B.,Vaishnav, A.,Patel, C.,Guy-Evans, H.,Herve, G.,Evans, D.R. Pressure-induced activation of latent dihydroorotase from Aquifex aeolicus as revealed by high pressure protein crystallography. Febs J., 286:1204-1213, 2019 Cited by PubMed Abstract: Dihydroorotase (DHOase) is involved in the de novo synthesis of pyrimidine in virtually all organisms, and it is usually associated with two other enzymes found in this biosynthetic pathway, carbamylphosphate synthetase and/or aspartate transcarbamylase (ATCase). In the hyperthermophilic bacterium Aquifex aeolicus, ATCase and DHOase are noncovalently associated. Upon dissociation, ATCase keeps its activity entirely while DHOase is totally inactivated. It was previously shown that high pressure fully restores the activity of this isolated DHOase. On the basis of kinetic studies, site-directed mutagenesis and the use of peptides mimicking loop A, a loop that appears to block access to the active site, was proposed that this pressure-induced reactivation was due to the decrease in the volume of the system, -ΔV, resulting from the disruption of known ionic interactions between the loop and the main part of the protein. In this study, this interpretation is more precisely demonstrated by the determination of the crystallographic structure of isolated DHOase under pressure. In addition to the loop displacements, pressure induces a discrete rearrangement of the catalytic site aspartate 305, an effect that might additionally contribute to the reactivation of this enzyme. PubMed: 30657257DOI: 10.1111/febs.14758 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.45 Å) |
Structure validation
Download full validation report
