What question did this study set out to answer?

To determine the electrostatic factors responsible for the remarkably low pKa of the catalytic cysteine within the conserved (H/V)CX5R(S/T) motif across diverse protein-tyrosine phosphatases.

March 31, 1998Biochemistry

Electrostatic Evaluation of the Signature Motif (H/V)CX5R(S/T) in Protein−Tyrosine Phosphatases

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Authors

GPGünther H. PetersTechnical University of Denmark TFThomas M. FrimurerUniversity of Copenhagen OOOle H. OlsenMC2 Therapeutics (Denmark)

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Implication

Electrostatic modeling study reveals backbone microdipoles drive the low active-site cysteine pKa across diverse protein-tyrosine phosphatases, highlighting structural mechanisms of catalysis.

Key Points

To determine the electrostatic factors responsible for the remarkably low pKa of the catalytic cysteine within the conserved (H/V)CX5R(S/T) motif across diverse protein-tyrosine phosphatases.
Evaluated four structurally divergent phosphatases with low sequence homology: bacterial Yersinia PTP, human PTP1B, human VHR, and bovine low molecular weight phosphatase.
Applied the single-site titration method based on Poisson-Boltzmann continuum electrostatics to quantify the electrostatic contribution of the active-site loop and neighboring residues.
The spatial architecture of the (H/V)CX5R(S/T) loop and microdipoles of backbone CONHCalpha atoms exert the primary electrostatic influence maintaining the low cysteine pKa.
Backbone microdipoles have a stronger stabilizing effect on the cysteine thiolate anion than the dipole generated by the central alpha-helix.
Interactions with other ionizable side chains are largely negligible, with the conserved arginine being the only residue that significantly stabilizes the ionized cysteine.

Cite This Study

Peters et al. (1998) studied this question.

synapsesocial.com/papers/6a7c55fb99c6d6845826b7e2 https://doi.org/10.1021/bi971187i

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Implication

Electrostatic modeling study reveals backbone microdipoles drive the low active-site cysteine pKa across diverse protein-tyrosine phosphatases, highlighting structural mechanisms of catalysis.

Electrostatic Evaluation of the Signature Motif (H/V)CX5R(S/T) in Protein−Tyrosine Phosphatases

Discussion

Member takes

Implication

Key Points

Cite This Study

Electrostatic Evaluation of the Signature Motif (H/V)CX5R(S/T) in Protein−Tyrosine Phosphatases

Discussion

Member takes

Implication

Key Points

Cite This Study

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