Mammalian Spermidine Synthase : Identification of Cysteine Residues and Investigation of the Putrescine Binding Site

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Author(s)

Abstract

Homology modeling and inhibitory studies using substrate analogs were undertaken to construct a possible three-dimensional structure, including the putrescine-binding site, of rat spermidine synthase based on its primary sequence. Of the ten cysteine residues of the enzyme, six residues were chemically determined as sulfhydryl; similarly, one residue (C25) was determined as the disulfide. Using the model obtained from the Swiss-Model protein-modeling server, and based on the crystal structure of the <i>Thermotoga maritima</i> enzyme, the three remaining residues were assigned as sulfhydryl. Discussions are presented on the counterpart of the C25 residue, based on the apparent role of the bacterial N-terminal peptide region in reinforcing the binding between protomers in a functional oligomeric form. The active sites of the bacterial and mammalian versions of the enzyme were very similar. The putrescine-binding site of the rat enzyme was investigated using IC<sub>50</sub> values of the analogs of two known potent inhibitors, <i>n</i>-butylamine and <i>trans</i>-4-methylcyclohexylamine (4MCHA). Our results indicated that 5-amino-1-pentene and 4MCHA possess comparable inhibitory activities towards the enzyme.

Journal

  • Biological and Pharmaceutical Bulletin

    Biological and Pharmaceutical Bulletin 27(9), 1327-1332, 2004-09-01

    The Pharmaceutical Society of Japan

References:  21

Cited by:  2

Codes

  • NII Article ID (NAID)
    110003608971
  • NII NACSIS-CAT ID (NCID)
    AA10885497
  • Text Lang
    ENG
  • Article Type
    Journal Article
  • ISSN
    09186158
  • NDL Article ID
    7056223
  • NDL Source Classification
    ZS51(科学技術--薬学)
  • NDL Call No.
    Z53-V41
  • Data Source
    CJP  CJPref  NDL  NII-ELS  J-STAGE 
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