2bnd: Difference between revisions

Bacterial UMP kinases are essential enzymes involved in the multistep, synthesis of nucleoside triphosphates. They are hexamers regulated by the, allosteric activator GTP and inhibited by UTP. We solved the crystal, structure of Escherichia coli UMP kinase bound to the UMP substrate (2.3 A, resolution), the UDP product (2.6 A), or UTP (2.45 A). The monomer fold, unrelated to that of other nucleoside monophosphate kinases, belongs to, the carbamate kinase-like superfamily. However, the phosphate acceptor, binding cleft and subunit assembly are characteristic of UMP kinase., Interactions with UMP explain the high specificity for this natural, substrate. UTP, previously described as an allosteric inhibitor, was, unexpectedly found in the phosphate acceptor site, suggesting that it acts, as a competitive inhibitor. Site-directed mutagenesis of residues Thr-138, and Asn-140, involved in both uracil recognition and active site, interaction within the hexamer, decreased the activation by GTP and, inhibition by UTP. These experiments suggest a cross-talk mechanism, between enzyme subunits involved in cooperative binding at the phosphate, acceptor site and in allosteric regulation by GTP. As bacterial UMP, kinases have no counterpart in eukaryotes, the information provided here, could help the design of new antibiotics.

2BND is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli] with UDP, POP and GOL as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Nucleoside-phosphate_kinase Nucleoside-phosphate kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.4.4 2.7.4.4] Structure known Active Site: AC1. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=2BND OCA].  

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