Related Experiment Video

Updated: Aug 10, 2026

Profiling of Methyltransferases and Other S-adenosyl-L-homocysteine-binding Proteins by Capture Compound Mass Spectrometry (CCMS)
17:12

Profiling of Methyltransferases and Other S-adenosyl-L-homocysteine-binding Proteins by Capture Compound Mass Spectrometry (CCMS)

Published on: December 20, 2010

Computational characterization of substrate binding and catalysis in S-adenosylhomocysteine hydrolase

Y Hu1, X Yang, D H Yin

  • 1Department of Pharmaceutical Chemistry, The University of Kansas, Lawrence, Kansas 66045-2106, USA. ybhu@ku.edu

Biochemistry
|December 12, 2001
PubMed

Insights

S-Adenosylhomocysteine (AdoHcy) hydrolase binds substrates specifically in its closed form, with the adenine moiety being key. Computational docking revealed key residues involved in substrate binding and catalysis for this essential enzyme.

Area of Science:

  • Biochemistry
  • Enzymology
  • Structural Biology

Background:

  • S-Adenosylhomocysteine (AdoHcy) hydrolase regulates cellular homocysteine levels and methyltransferase activity.
  • The enzyme exists in open (unoccupied active site) and closed (occupied active site) conformations.
  • Understanding substrate binding is crucial for enzyme mechanism elucidation.

Purpose of the Study:

  • To investigate the binding modes of natural substrates to AdoHcy hydrolase using computational methods.
  • To identify key amino acid residues involved in substrate recognition and catalysis.
  • To elucidate the role of enzyme conformation in substrate specificity.

Main Methods:

  • Computational docking using AutoDock.
  • Molecular dynamics simulations using CHARMM for confirmation.
  • Analysis of enzyme-substrate interactions in both open and closed conformations.

Main Results:

  • Substrate binding to the open enzyme form is nonspecific.
  • Binding to the closed enzyme form is highly specific, primarily recognizing the adenine moiety.
  • Identified key residues (e.g., Thr57, Glu59, His55, Asp131) involved in binding and catalysis.
  • The homocysteine moiety binds in a strained conformation, potentially enhancing catalysis.

Conclusions:

  • Enzyme conformation dictates substrate binding specificity.
  • Specific residues play critical roles in substrate recognition and the catalytic mechanism.
  • Computational modeling provides valuable insights into enzyme function and substrate interactions.

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