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Substrate-shielding and hydrolytic reaction in hydrolases.

Yusuke Kanematsu1, Ryotaro Koike, Takayuki Amemiya

  • 1Department of Complex Systems Science, Graduate School of Information Science, Nagoya University, Nagoya 464-8601, Japan.

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Hydrolase enzymes shield substrates differently based on their reaction mechanism. Double displacement and exo hydrolases show more substrate shielding compared to single displacement and endo hydrolases, impacting function.

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Area of Science:

  • Enzymology
  • Structural Biology
  • Biochemistry

Background:

  • Transferase enzymes shield substrates from water via large structural changes.
  • Hydrolase enzymes typically expose substrates to water with minimal structural changes.
  • Some hydrolases, however, deeply bury their substrates within the protein structure.

Purpose of the Study:

  • To investigate the relationship between substrate-shielding and enzymatic functions in hydrolases.
  • To examine the extent of substrate accessibility within 70 representative hydrolase structures.

Main Methods:

  • Analysis of 70 representative hydrolase structures.
  • Quantification of relative accessible surface areas of substrates within the enzyme active sites.

Main Results:

  • Hydrolases employing a double displacement reaction mechanism bury substrates more deeply than those using single displacement.
  • Exo hydrolases exhibit significantly greater substrate shielding from water compared to endo hydrolases.

Conclusions:

  • Substrate-shielding in hydrolases is linked to the specific chemical reaction mechanism.
  • The degree of substrate shielding correlates with the enzyme's substrate specificity.