2bmu
UMP KINASE FROM PYROCOCCUS FURIOSUS COMPLEXED WITH ITS SUBSTRATE UMP AND ITS SUBSTRATE ANALOG AMPPNP
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OverviewOverview
UMP kinase (UMPK), the enzyme responsible for microbial UMP, phosphorylation, plays a key role in pyrimidine nucleotide biosynthesis, regulating this process via feed-back control and via gene repression of, carbamoyl phosphate synthetase (the first enzyme of the pyrimidine, biosynthesis pathway). We present crystal structures of Pyrococcus, furiosus UMPK, free or complexed with AMPPNP or AMPPNP and UMP, at 2.4 A, 3 A and 2.55 A resolution, respectively, providing a true snapshot of the, catalytically competent bisubstrate complex. The structure proves that, UMPK does not resemble other nucleoside monophosphate kinases, including, the UMP/CMP kinase found in animals, and thus UMPK may be a potential, antimicrobial target. This enzyme has a homohexameric architecture centred, around a hollow nucleus, and is organized as a trimer of dimers. The UMPK, polypeptide exhibits the amino acid kinase family (AAKF) fold that has, been reported in carbamate kinase and acetylglutamate kinase. Comparison, with acetylglutamate kinase reveals that the substrates bind within each, subunit at equivalent, adequately adapted sites. The UMPK structure, contains two bound Mg ions, of which one helps stabilize the transition, state, thus having the same catalytic role as one lysine residue found in, acetylglutamate kinase, which is missing from P.furiosus UMPK. Relative to, carbamate kinase and acetylglutamate kinase, UMPK presents a radically, different dimer architecture, lacking the characteristic 16-stranded, beta-sheet backbone that was considered a signature of AAKF enzymes. Its, hexameric architecture, also a novel trait, results from equatorial, contacts between the A and B subunits of adjacent dimers combined with, polar contacts between A or B subunits, and may be required for the UMPK, regulatory functions, such as gene regulation, proposed here to be, mediated by hexamer-hexamer interactions with the DNA-binding protein, PepA.
About this StructureAbout this Structure
2BMU is a Single protein structure of sequence from Pyrococcus furiosus with MG, ANP and U5P as ligands. Structure known Active Site: AC1. Full crystallographic information is available from OCA.
ReferenceReference
The crystal structure of Pyrococcus furiosus UMP kinase provides insight into catalysis and regulation in microbial pyrimidine nucleotide biosynthesis., Marco-Marin C, Gil-Ortiz F, Rubio V, J Mol Biol. 2005 Sep 16;352(2):438-54. PMID:16095620
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