Crystal structure of Methanococcus jannaschii dihydroorotase

Vitali, Jacqueline; Nix, Jay C.; Newman, Haley E.; Colaneri, Michael J.

doi:10.1002/prot.26412

Crystal structure of Methanococcus jannaschii dihydroorotase

Journal Article · Wed Aug 17 00:00:00 EDT 2022 · Proteins

DOI:https://doi.org/10.1002/prot.26412· OSTI ID:2470689

^[1]; ^[2]; Newman, Haley E. ^[1]; ^[3]

Cleveland State Univ., Cleveland, OH (United States)
Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States). Advanced Light Source (ALS)
State Univ. of New York (SUNY), Old Westbury, NY (United States)

In this paper, we report the structural analysis of dihydroorotase (DHOase) from the hyperthermophilic and barophilic archaeon Methanococcus jannaschii. DHOase catalyzes the reversible cyclization of N-carbamoyl-l-aspartate to l-dihydroorotate in the third step of de novo pyrimidine biosynthesis. DHOases form a very diverse family of enzymes and have been classified into types and subtypes with structural similarities and differences among them. This is the first archaeal DHOase studied by x-ray diffraction. Its structure and comparison with known representatives of the other subtypes help define the structural features of the archaeal subtype. The M. jannaschii DHOase is found here to have traits from all subtypes. Contrary to expectations, it has a carboxylated lysine bridging the two Zn ions in the active site, and a long catalytic loop. It is a monomeric protein with a large β sandwich domain adjacent to the TIM barrel. Loop 5 is similar to bacterial type III and the C-terminal extension is long.

View Accepted Manuscript (DOE)

Research Organization:: Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)

Sponsoring Organization:: National Institutes of Health (NIH); USDOE

Grant/Contract Number:: AC02-05CH11231

OSTI ID:: 2470689

Journal Information:: Proteins, Journal Name: Proteins Journal Issue: 1 Vol. 91; ISSN 0887-3585

Publisher:: WileyCopyright Statement

Country of Publication:: United States

Language:: English

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59 BASIC BIOLOGICAL SCIENCES
Methanococcus jannaschii
crystal structure
dihydroorotase
pyrimidine biosynthesis

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References (32)

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