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== Function == | == Function == | ||
[[http://www.uniprot.org/uniprot/KAD_AQUAE KAD_AQUAE]] Catalyzes the reversible transfer of the terminal phosphate group between ATP and AMP. This small ubiquitous enzyme involved in the energy metabolism and nucleotide synthesis, is essential for maintenance and cell growth (By similarity). | [[http://www.uniprot.org/uniprot/KAD_AQUAE KAD_AQUAE]] Catalyzes the reversible transfer of the terminal phosphate group between ATP and AMP. This small ubiquitous enzyme involved in the energy metabolism and nucleotide synthesis, is essential for maintenance and cell growth (By similarity). | ||
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== Publication Abstract from PubMed == | |||
Kinases perform phosphoryl-transfer reactions in milliseconds; without enzymes, these reactions would take about 8,000 years under physiological conditions. Despite extensive studies, a comprehensive understanding of kinase energy landscapes, including both chemical and conformational steps, is lacking. Here we scrutinize the microscopic steps in the catalytic cycle of adenylate kinase, through a combination of NMR measurements during catalysis, pre-steady-state kinetics, molecular-dynamics simulations and crystallography of active complexes. We find that the Mg2+ cofactor activates two distinct molecular events: phosphoryl transfer (>105-fold) and lid opening (103-fold). In contrast, mutation of an essential active site arginine decelerates phosphoryl transfer 103-fold without substantially affecting lid opening. Our results highlight the importance of the entire energy landscape in catalysis and suggest that adenylate kinases have evolved to activate key processes simultaneously by precise placement of a single, charged and very abundant cofactor in a preorganized active site. | |||
The energy landscape of adenylate kinase during catalysis.,Kerns SJ, Agafonov RV, Cho YJ, Pontiggia F, Otten R, Pachov DV, Kutter S, Phung LA, Murphy PN, Thai V, Alber T, Hagan MF, Kern D Nat Struct Mol Biol. 2015 Jan 12. doi: 10.1038/nsmb.2941. PMID:25580578<ref>PMID:25580578</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
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== References == | |||
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Revision as of 14:01, 28 January 2015
Cobalt between two ADP's in the active site of adenylate kinaseCobalt between two ADP's in the active site of adenylate kinase
Structural highlights
Function[KAD_AQUAE] Catalyzes the reversible transfer of the terminal phosphate group between ATP and AMP. This small ubiquitous enzyme involved in the energy metabolism and nucleotide synthesis, is essential for maintenance and cell growth (By similarity). Publication Abstract from PubMedKinases perform phosphoryl-transfer reactions in milliseconds; without enzymes, these reactions would take about 8,000 years under physiological conditions. Despite extensive studies, a comprehensive understanding of kinase energy landscapes, including both chemical and conformational steps, is lacking. Here we scrutinize the microscopic steps in the catalytic cycle of adenylate kinase, through a combination of NMR measurements during catalysis, pre-steady-state kinetics, molecular-dynamics simulations and crystallography of active complexes. We find that the Mg2+ cofactor activates two distinct molecular events: phosphoryl transfer (>105-fold) and lid opening (103-fold). In contrast, mutation of an essential active site arginine decelerates phosphoryl transfer 103-fold without substantially affecting lid opening. Our results highlight the importance of the entire energy landscape in catalysis and suggest that adenylate kinases have evolved to activate key processes simultaneously by precise placement of a single, charged and very abundant cofactor in a preorganized active site. The energy landscape of adenylate kinase during catalysis.,Kerns SJ, Agafonov RV, Cho YJ, Pontiggia F, Otten R, Pachov DV, Kutter S, Phung LA, Murphy PN, Thai V, Alber T, Hagan MF, Kern D Nat Struct Mol Biol. 2015 Jan 12. doi: 10.1038/nsmb.2941. PMID:25580578[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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