Coupling protein dynamics to reaction center electron density in enzymes

An electronic protein promoting vibration in human purine nucleoside phosphorylase

Joshua S. Mincer, Sara Nuñez, Steven D Schwartz

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

The notable three oxygen stacking that occurs upon binding of ribonucleoside substrate and phosphate nucleophile by human purine nucleoside phosphorylase (hPNP) enables the coupling of protein dynamic modes to compress this stack, squeezing the ribosyl O4′ between ribosyl O5′ and the nuclophilic OP. Created primarily by the motion of active site residue H257, this compression dynamically lowers the barrier height for N9-C1′ ribosidic bond cleavage by as much as 20%. As such, this compression constitutes a protein promoting vibration (PPV) (S. Nuñez et al.). Presently, we demonstrate charge fluctuations in the ribose and purine components of the ribonucleoside substrate, as well as specifically across the N9-C1′ ribosidic bond, that are correlated with the PPV and can explain the decrease in reaction barrier height due to their facilitating cleavage of the ribosidic bond. hPNP apparently employs protein dynamics to push electrons, a finding that suggests that this coupling may be found more generally in enzymes that catalyze substitution and elimination reactions.

Original languageEnglish (US)
Pages (from-to)501-509
Number of pages9
JournalJournal of Theoretical and Computational Chemistry
Volume3
Issue number4
DOIs
StatePublished - Dec 2004
Externally publishedYes

Fingerprint

Purine-Nucleoside Phosphorylase
purines
nucleosides
Carrier concentration
enzymes
Enzymes
Ribonucleosides
proteins
Proteins
vibration
electronics
cleavage
ribose
Nucleophiles
Ribose
nucleophiles
Substrates
compressing
elimination
phosphates

Keywords

  • Catalysis
  • Mechanism
  • Protein dynamics

ASJC Scopus subject areas

  • Physical and Theoretical Chemistry

Cite this

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title = "Coupling protein dynamics to reaction center electron density in enzymes: An electronic protein promoting vibration in human purine nucleoside phosphorylase",
abstract = "The notable three oxygen stacking that occurs upon binding of ribonucleoside substrate and phosphate nucleophile by human purine nucleoside phosphorylase (hPNP) enables the coupling of protein dynamic modes to compress this stack, squeezing the ribosyl O4′ between ribosyl O5′ and the nuclophilic OP. Created primarily by the motion of active site residue H257, this compression dynamically lowers the barrier height for N9-C1′ ribosidic bond cleavage by as much as 20{\%}. As such, this compression constitutes a protein promoting vibration (PPV) (S. Nu{\~n}ez et al.). Presently, we demonstrate charge fluctuations in the ribose and purine components of the ribonucleoside substrate, as well as specifically across the N9-C1′ ribosidic bond, that are correlated with the PPV and can explain the decrease in reaction barrier height due to their facilitating cleavage of the ribosidic bond. hPNP apparently employs protein dynamics to push electrons, a finding that suggests that this coupling may be found more generally in enzymes that catalyze substitution and elimination reactions.",
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T2 - An electronic protein promoting vibration in human purine nucleoside phosphorylase

AU - Mincer, Joshua S.

AU - Nuñez, Sara

AU - Schwartz, Steven D

PY - 2004/12

Y1 - 2004/12

N2 - The notable three oxygen stacking that occurs upon binding of ribonucleoside substrate and phosphate nucleophile by human purine nucleoside phosphorylase (hPNP) enables the coupling of protein dynamic modes to compress this stack, squeezing the ribosyl O4′ between ribosyl O5′ and the nuclophilic OP. Created primarily by the motion of active site residue H257, this compression dynamically lowers the barrier height for N9-C1′ ribosidic bond cleavage by as much as 20%. As such, this compression constitutes a protein promoting vibration (PPV) (S. Nuñez et al.). Presently, we demonstrate charge fluctuations in the ribose and purine components of the ribonucleoside substrate, as well as specifically across the N9-C1′ ribosidic bond, that are correlated with the PPV and can explain the decrease in reaction barrier height due to their facilitating cleavage of the ribosidic bond. hPNP apparently employs protein dynamics to push electrons, a finding that suggests that this coupling may be found more generally in enzymes that catalyze substitution and elimination reactions.

AB - The notable three oxygen stacking that occurs upon binding of ribonucleoside substrate and phosphate nucleophile by human purine nucleoside phosphorylase (hPNP) enables the coupling of protein dynamic modes to compress this stack, squeezing the ribosyl O4′ between ribosyl O5′ and the nuclophilic OP. Created primarily by the motion of active site residue H257, this compression dynamically lowers the barrier height for N9-C1′ ribosidic bond cleavage by as much as 20%. As such, this compression constitutes a protein promoting vibration (PPV) (S. Nuñez et al.). Presently, we demonstrate charge fluctuations in the ribose and purine components of the ribonucleoside substrate, as well as specifically across the N9-C1′ ribosidic bond, that are correlated with the PPV and can explain the decrease in reaction barrier height due to their facilitating cleavage of the ribosidic bond. hPNP apparently employs protein dynamics to push electrons, a finding that suggests that this coupling may be found more generally in enzymes that catalyze substitution and elimination reactions.

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