Literature Review

DHPS



NAD Dependent Enzyme Binding

Spermadine-enzyme binding is dependent on NAD and the maximum binding for NAD and spermidine is 4 molecules/enzyme tetramer.

  • A new crystal structure of deoxyhypusine synthase reveals the configuration of the active enzyme and of an enzyme.NAD.inhibitor ternary complex. (PMID: 15100216,(ncbi.nlm.nih.gov)) Umland T.C. … Davies D.R. J. Biol. Chem. 2004 3 4 22 64
    • The first structure of a deoxyhypusine synthase·NAD·inhibitor ternary complex under physiological conditions. It provides a structural context to discuss the results of previous biochemical investigations of the deoxyhypusine synthase reaction mechanism.
  • Structure-function studies of human deoxyhypusine synthase: identification of amino acid residues critical for the binding of spermidine and NAD. (PMID: 11311149,(ncbi.nlm.nih.gov)) Lee C.H. … Park M.H. Biochem. J. 2001 4 22 64
    • This study showed that NAD-site mutant enzymes had a reduced binding of spermidine, so spermidine binding is likely dependent on NAD.
  • Human deoxyhypusine synthase: interrelationship between binding of NAD and substrates. (PMID: 11104695,(ncbi.nlm.nih.gov)) Lee C.H. … Park M.H. Biochem. J. 2000 22 64
    • The maximum binding for NAD and spermidine was estimated to be approximately 4 molecules each/enzyme tetramer.
  • Deoxyhypusine synthase generates and uses bound NADH in a transient hydride transfer mechanism. (PMID: 10734052,(ncbi.nlm.nih.gov)) Wolff E.C. … Park M.H. J. Biol. Chem. 2000 22 64
    • The number of NADH molecules bound approached four/enzyme tetramer; not all of the bound NADH was available for reduction of the eIF5A-imine intermediate.
  • Complex formation between deoxyhypusine synthase and its protein substrate, the eukaryotic translation initiation factor 5A (eIF5A) precursor. (PMID: 10229683,(ncbi.nlm.nih.gov)) Lee Y.B. … Park M.H.Biochem. J. 1999 3 22 64
    • The formation of a stable complex between human DHPS and its protein substrate eIF5A, was examined by affinity chromatography. Formation of the complex was not dependent on NAD+ or spermidine and occurred at pH7.0-9.2.
  • Crystal structure of the NAD complex of human deoxyhypusine synthase: an enzyme with a ball-and-chain mechanism for blocking the active site. (PMID: 9493264,(ncbi.nlm.nih.gov)) Liao D.-I. … Davies D.R. Structure 1998 3 4 22 64
    • The active site of DHPS is below the surface of the enzyme and is inaccessible. The reaction steps carried out by the enzyme must be accompanied by significant conformational changes, including displacement of the alpha helix.
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