6f7u

Molecular Mechanism of ATP versus GTP Selectivity of Adenylate KinaseMolecular Mechanism of ATP versus GTP Selectivity of Adenylate Kinase

Structural highlights 6f7u is a 1 chain structure with sequence from Ecoli. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: , Gene: adk, EC55989_0487 (ECOLI) Activity: Adenylate kinase, with EC number 2.7.4.3 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [KAD_ECO55] Catalyzes the reversible transfer of the terminal phosphate group between ATP and AMP. Plays an important role in cellular energy homeostasis and in adenine nucleotide metabolism. Publication Abstract from PubMed Enzymatic substrate selectivity is critical for the precise control of metabolic pathways. In cases where chemically related substrates are present inside cells, robust mechanisms of substrate selectivity are required. Here, we report the mechanism utilized for catalytic ATP versus GTP selectivity during adenylate kinase (Adk) -mediated phosphorylation of AMP. Using NMR spectroscopy we found that while Adk adopts a catalytically competent and closed structural state in complex with ATP, the enzyme is arrested in a catalytically inhibited and open state in complex with GTP. X-ray crystallography experiments revealed that the interaction interfaces supporting ATP and GTP recognition, in part, are mediated by coinciding residues. The mechanism provides an atomic view on how the cellular GTP pool is protected from Adk turnover, which is important because GTP has many specialized cellular functions. In further support of this mechanism, a structure-function analysis enabled by synthesis of ATP analogs suggests that a hydrogen bond between the adenine moiety and the backbone of the enzyme is vital for ATP selectivity. The importance of the hydrogen bond for substrate selectivity is likely general given the conservation of its location and orientation across the family of eukaryotic protein kinases. Molecular mechanism of ATP versus GTP selectivity of adenylate kinase.,Rogne P, Rosselin M, Grundstrom C, Hedberg C, Sauer UH, Wolf-Watz M Proc Natl Acad Sci U S A. 2018 Mar 5. pii: 1721508115. doi:, 10.1073/pnas.1721508115. PMID:29507216 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

spinqualitylabelsall models 6f7u, resolution 1.40Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image