The pH dependence of stability of the activation helix and the catalytic site of GART

Dimitrios Morikis; Adrian H Elcock; Patricia A Jennings; J.Andrew McCammon

doi:10.1016/S0301-4622(03)00079-6

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The pH dependence of stability of the activation helix and the catalytic site of GART

Journal article

Peer reviewed

The pH dependence of stability of the activation helix and the catalytic site of GART

Dimitrios Morikis, Adrian H Elcock, Patricia A Jennings and J.Andrew McCammon

Biophysical chemistry, Vol.105(2), pp.279-291

2003

DOI: 10.1016/S0301-4622(03)00079-6

PMID: 14499900

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Abstract

We have predicted the free energy of unfolding for the pH-dependent helix-coil transition of the activation helix of GART using continuum electrostatic calculations and structural modeling. We have assigned the contributions of each element of secondary structure and of each ionizable residue, within and in the vicinity of the activation helix, to the stability of several fragments of GART that participate in the formation of the catalytic site. We demonstrate that the interaction of His121–His132 contributes 2.2 kcal/mol to the ionization free energy between pH 0 and approximately 6. We also show that the ionization state of a network of five histidines, His108, His119, His121, His132 and His137, and two aspartic acids Asp141 and Asp144, contributes approximately 12 kcal/mol to the stability of the catalytic site of GART, out of a total stability of 16 kcal/mol of the whole enzyme. These interactions are important for the formation of the catalytic site of GART.

Electrostatic calculations

Glycinamide ribonucleotide transformylase

Stability

p Ka

Poisson–Boltzmann

Helix–coil transition

GART

Details

Title: Subtitle: The pH dependence of stability of the activation helix and the catalytic site of GART
Creators: Dimitrios Morikis - Department of Chemical and Environmental Engineering, University of California at Riverside, Riverside, CA 92521, USA
Adrian H Elcock - Department of Biochemistry, University of Iowa, Iowa City, IA 52242, USA
Patricia A Jennings - Department of Chemistry and Biochemistry, University of California at San Diego, La Jolla, CA 92093, USA
J.Andrew McCammon - Department of Chemistry and Biochemistry, University of California at San Diego, La Jolla, CA 92093, USA
Resource Type: Journal article
Publication Details: Biophysical chemistry, Vol.105(2), pp.279-291
Publisher: Elsevier B.V
DOI: 10.1016/S0301-4622(03)00079-6
PMID: 14499900
ISSN: 0301-4622
eISSN: 1873-4200
Language: English
Date published: 2003
Academic Unit: Physics and Astronomy; Biochemistry and Molecular Biology
Record Identifier: 9984025399902771

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