Abstract
Yersinia protein tyrosine phosphatase (YopH) is the most efficient enzyme among all PTPases. YopH is hyperactive compared to human PTPases, interfering with mammalian cellular pathways to achieve the pathogenicity of Yersinia. Two properties related to the catalytic loop structure differences have been proposed to affect its dynamics and enzyme efficiency. One is the ability of the loop to form stabilizing interactions to bound ligand after loop closure, which has long been recognized. In addition, the loop flexibility/mobility was suggested in a previous study to be a factor as well, based on the observation that incremental changes in PTPase loop structure by single point mutations to alanine often induce incremental changes in enzyme catalytic efficiency. In this study, the temperature jump relaxation spectroscopy (T-jump) has been used to discern the subtle changes of the loop dynamics due to point loop mutations. As expected, our results suggest a correlation between loop dynamics and the size of the residue on the catalytic loop. The stabilization of the enzyme-ligand complex is often enthalpy driven, achieved by formation of additional favorable hydrogen bonding/ionic interactions after loop closure. Interestingly, our T-jump and X-ray crystallography studies on YopH suggest that the elimination of some ligand-protein interactions by mutation does not necessarily destabilize the ligand-enzyme complex after loop closure, since the increased entropy in the forms of more mobile protein residues may be sufficient to compensate the free energy loss due to lost interactions and may even lead to enhanced efficiency of the enzyme catalysis. How these competing loop properties may affect loop dynamics and enzyme function are discussed.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 6166-6176 |
| Number of pages | 11 |
| Journal | Journal of Physical Chemistry B |
| Volume | 116 |
| Issue number | 21 |
| DOIs | |
| State | Published - May 31 2012 |
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ASJC Scopus subject areas
- Physical and Theoretical Chemistry
- Materials Chemistry
- Surfaces, Coatings and Films
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Investigation of catalytic loop structure, dynamics, and function relationship of Yersinia protein tyrosine phosphatase by temperature-jump relaxation spectroscopy and X-ray structural determination. / Ke, Shan; Ho, Meng Chiao; Zhadin, Nickolay; Deng, Hua; Callender, Robert.
In: Journal of Physical Chemistry B, Vol. 116, No. 21, 31.05.2012, p. 6166-6176.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Investigation of catalytic loop structure, dynamics, and function relationship of Yersinia protein tyrosine phosphatase by temperature-jump relaxation spectroscopy and X-ray structural determination
AU - Ke, Shan
AU - Ho, Meng Chiao
AU - Zhadin, Nickolay
AU - Deng, Hua
AU - Callender, Robert
PY - 2012/5/31
Y1 - 2012/5/31
N2 - Yersinia protein tyrosine phosphatase (YopH) is the most efficient enzyme among all PTPases. YopH is hyperactive compared to human PTPases, interfering with mammalian cellular pathways to achieve the pathogenicity of Yersinia. Two properties related to the catalytic loop structure differences have been proposed to affect its dynamics and enzyme efficiency. One is the ability of the loop to form stabilizing interactions to bound ligand after loop closure, which has long been recognized. In addition, the loop flexibility/mobility was suggested in a previous study to be a factor as well, based on the observation that incremental changes in PTPase loop structure by single point mutations to alanine often induce incremental changes in enzyme catalytic efficiency. In this study, the temperature jump relaxation spectroscopy (T-jump) has been used to discern the subtle changes of the loop dynamics due to point loop mutations. As expected, our results suggest a correlation between loop dynamics and the size of the residue on the catalytic loop. The stabilization of the enzyme-ligand complex is often enthalpy driven, achieved by formation of additional favorable hydrogen bonding/ionic interactions after loop closure. Interestingly, our T-jump and X-ray crystallography studies on YopH suggest that the elimination of some ligand-protein interactions by mutation does not necessarily destabilize the ligand-enzyme complex after loop closure, since the increased entropy in the forms of more mobile protein residues may be sufficient to compensate the free energy loss due to lost interactions and may even lead to enhanced efficiency of the enzyme catalysis. How these competing loop properties may affect loop dynamics and enzyme function are discussed.
AB - Yersinia protein tyrosine phosphatase (YopH) is the most efficient enzyme among all PTPases. YopH is hyperactive compared to human PTPases, interfering with mammalian cellular pathways to achieve the pathogenicity of Yersinia. Two properties related to the catalytic loop structure differences have been proposed to affect its dynamics and enzyme efficiency. One is the ability of the loop to form stabilizing interactions to bound ligand after loop closure, which has long been recognized. In addition, the loop flexibility/mobility was suggested in a previous study to be a factor as well, based on the observation that incremental changes in PTPase loop structure by single point mutations to alanine often induce incremental changes in enzyme catalytic efficiency. In this study, the temperature jump relaxation spectroscopy (T-jump) has been used to discern the subtle changes of the loop dynamics due to point loop mutations. As expected, our results suggest a correlation between loop dynamics and the size of the residue on the catalytic loop. The stabilization of the enzyme-ligand complex is often enthalpy driven, achieved by formation of additional favorable hydrogen bonding/ionic interactions after loop closure. Interestingly, our T-jump and X-ray crystallography studies on YopH suggest that the elimination of some ligand-protein interactions by mutation does not necessarily destabilize the ligand-enzyme complex after loop closure, since the increased entropy in the forms of more mobile protein residues may be sufficient to compensate the free energy loss due to lost interactions and may even lead to enhanced efficiency of the enzyme catalysis. How these competing loop properties may affect loop dynamics and enzyme function are discussed.
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U2 - 10.1021/jp3037846
DO - 10.1021/jp3037846
M3 - Article
VL - 116
SP - 6166
EP - 6176
JO - Journal of Physical Chemistry B Materials
JF - Journal of Physical Chemistry B Materials
SN - 1520-6106
IS - 21
ER -