4CF7

Crystal structure of adenylate kinase from Aquifex aeolicus with MgADP bound

Summary for 4CF7

• Entry DOI: 10.2210/pdb4cf7/pdb
• Descriptor: ADENYLATE KINASE, ADENOSINE-5'-DIPHOSPHATE, ADENOSINE MONOPHOSPHATE, ... (5 entities in total)
• Functional Keywords: transferase, phosphoryl transfer, nucleotide-binding
• Biological source: AQUIFEX AEOLICUS
• Total number of polymer chains: 2
• Total formula weight: 48618.44

Authors

Kerns, S.J.,Agafonov, R.V.,Cho, Y.-J.,Pontiggia, F.,Otten, R.,Pachov, D.V.,Kutter, S.,Phung, L.A.,Murphy, P.N.,Thai, V.,Hagan, M.F.,Kern, D. (deposition date: 2013-11-13, release date: 2014-12-03, Last modification date: 2023-12-20)

Primary citation

Kerns, S.J.,Agafonov, R.V.,Cho, Y.,Pontiggia, F.,Otten, R.,Pachov, D.V.,Kutter, S.,Phung, L.A.,Murphy, P.N.,Thai, V.,Alber, T.,Hagan, M.F.,Kern, D.
The Energy Landscape of Adenylate Kinase During Catalysis.
Nat.Struct.Mol.Biol., 22:124-, 2015

PubMed Abstract: 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 Mg(2+) cofactor activates two distinct molecular events: phosphoryl transfer (>10(5)-fold) and lid opening (10(3)-fold). In contrast, mutation of an essential active site arginine decelerates phosphoryl transfer 10(3)-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.

PubMed: 25580578
DOI: 10.1038/NSMB.2941

Experimental method

X-RAY DIFFRACTION (1.594 Å)