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Insights into the phosphoryl transfer catalyzed by cAMP-dependent protein kinase: an X-ray crystallographic study of complexes with various metals and peptide substrate SP20.

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Gerlits O, Waltman MJ, Taylor S, Langan P, Kovalevsky A
OpenAccess logo Biochemistry 52 3721-7 (2013)
Related entries: 4iac, 4iad, 4iai, 4iak, 4iay, 4iaz

Cited: 18 times
EuropePMC logo PMID: 23672593

Abstract

X-ray structures of several ternary substrate and product complexes of the catalytic subunit of cAMP-dependent protein kinase (PKAc) have been determined with different bound metal ions. In the PKAc complexes, Mg(2+), Ca(2+), Sr(2+), and Ba(2+) metal ions could bind to the active site and facilitate the phosphoryl transfer reaction. ATP and a substrate peptide (SP20) were modified, and the reaction products ADP and the phosphorylated peptide were found trapped in the enzyme active site. Finally, we determined the structure of a pseudo-Michaelis complex containing Mg(2+), nonhydrolyzable AMP-PCP (β,γ-methyleneadenosine 5'-triphosphate) and SP20. The product structures together with the pseudo-Michaelis complex provide snapshots of different stages of the phosphorylation reaction. Comparison of these structures reveals conformational, coordination, and hydrogen bonding changes that might occur during the reaction and shed new light on its mechanism, roles of metals, and active site residues.

Articles - 4iaf mentioned but not cited (3)

  1. Insights into the phosphoryl transfer catalyzed by cAMP-dependent protein kinase: an X-ray crystallographic study of complexes with various metals and peptide substrate SP20. Gerlits O, Waltman MJ, Taylor S, Langan P, Kovalevsky A. Biochemistry 52 3721-3727 (2013)
  2. Determining the Functions of HIV-1 Tat and a Second Magnesium Ion in the CDK9/Cyclin T1 Complex: A Molecular Dynamics Simulation Study. Jin HX, Go ML, Yin P, Qiu XT, Zhu P, Yan XJ. PLoS ONE 10 e0124673 (2015)
  3. Globally correlated conformational entropy underlies positive and negative cooperativity in a kinase's enzymatic cycle. Wang Y, V S M, Kim J, Li G, Ahuja LG, Aoto P, Taylor SS, Veglia G. Nat Commun 10 799 (2019)


Reviews citing this publication (1)

  1. Molecular mechanisms of asymmetric RAF dimer activation. Jambrina PG, Bohuszewicz O, Buchete NV, Kolch W, Rosta E. Biochem. Soc. Trans. 42 784-790 (2014)

Articles citing this publication (14)

  1. Divalent Metal Ions Mg²⁺ and Ca²⁺ Have Distinct Effects on Protein Kinase A Activity and Regulation. Knape MJ, Ahuja LG, Bertinetti D, Burghardt NC, Zimmermann B, Taylor SS, Herberg FW. ACS Chem. Biol. 10 2303-2315 (2015)
  2. Metal-free cAMP-dependent protein kinase can catalyze phosphoryl transfer. Gerlits O, Das A, Keshwani MM, Taylor S, Waltman MJ, Langan P, Heller WT, Kovalevsky A. Biochemistry 53 3179-3186 (2014)
  3. Phosphoryl Transfer Reaction Snapshots in Crystals: INSIGHTS INTO THE MECHANISM OF PROTEIN KINASE A CATALYTIC SUBUNIT. Gerlits O, Tian J, Das A, Langan P, Heller WT, Kovalevsky A. J. Biol. Chem. 290 15538-15548 (2015)
  4. A QM/MM study of the associative mechanism for the phosphorylation reaction catalyzed by protein kinase A and its D166A mutant. Pérez-Gallegos A, Garcia-Viloca M, González-Lafont À, Lluch JM. J Comput Aided Mol Des 28 1077-1091 (2014)
  5. Uncoupling Catalytic and Binding Functions in the Cyclic AMP-Dependent Protein Kinase A. Kim J, Li G, Walters MA, Taylor SS, Veglia G. Structure 24 353-363 (2016)
  6. A QM/MM study of Kemptide phosphorylation catalyzed by protein kinase A. The role of Asp166 as a general acid/base catalyst. Pérez-Gallegos A, Garcia-Viloca M, González-Lafont À, Lluch JM. Phys Chem Chem Phys 17 3497-3511 (2015)
  7. Antibiotic Binding Drives Catalytic Activation of Aminoglycoside Kinase APH(2″)-Ia. Caldwell SJ, Huang Y, Berghuis AM. Structure 24 935-945 (2016)
  8. Distinct structural mechanisms determine substrate affinity and kinase activity of protein kinase Cα. Lee S, Devamani T, Song HD, Sandhu M, Larsen A, Sommese R, Jain A, Vaidehi N, Sivaramakrishnan S. J. Biol. Chem. 292 16300-16309 (2017)
  9. Protein Kinase A Catalytic Subunit Primed for Action: Time-Lapse Crystallography of Michaelis Complex Formation. Das A, Gerlits O, Parks JM, Langan P, Kovalevsky A, Heller WT. Structure 23 2331-2340 (2015)
  10. Theoretical studies of cyclic adenosine monophosphate dependent protein kinase: native enzyme and ground-state and transition-state analogues. Leigh KN, Webster CE. Dalton Trans 43 3039-3043 (2014)
  11. Understanding how cAMP-dependent protein kinase can catalyze phosphoryl transfer in the presence of Ca2+ and Sr2+: a QM/MM study. Pérez-Gallegos A, Garcia-Viloca M, González-Lafont À, Lluch JM. Phys Chem Chem Phys 19 10377-10394 (2017)
  12. Molecular-dynamics simulation methods for macromolecular crystallography. Wych DC, Aoto PC, Vu L, Wolff AM, Mobley DL, Fraser JS, Taylor SS, Wall ME. Acta Crystallogr D Struct Biol 79 50-65 (2023)
  13. Protein kinase A in the neutron beam: Insights for catalysis from directly observing protons. Gerlits O, Weiss KL, Blakeley MP, Veglia G, Taylor SS, Kovalevsky A. Methods Enzymol 634 311-331 (2020)
  14. Zooming in on protons: Neutron structure of protein kinase A trapped in a product complex. Gerlits O, Weiss KL, Blakeley MP, Veglia G, Taylor SS, Kovalevsky A. Sci Adv 5 eaav0482 (2019)


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