Kinetic Isotope Effect in the Unfolding of a Protein Secondary Structure: Calculations for Beta-Sheet Polyglycine Dimers as a Model
In the present work, we performed calculations of the kinetic isotope effect (KIE) on H/D, <sup>14</sup>N/<sup>15</sup>N, <sup>16</sup>O/<sup>18</sup>O, and <sup>12</sup>C/<sup>13</sup>C isotopic substitution in the dissociation...
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2025-01-01
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| author | Alexey O. Yanshin Vitaly G. Kiselev Alexey V. Baklanov |
| author_facet | Alexey O. Yanshin Vitaly G. Kiselev Alexey V. Baklanov |
| author_sort | Alexey O. Yanshin |
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| description | In the present work, we performed calculations of the kinetic isotope effect (KIE) on H/D, <sup>14</sup>N/<sup>15</sup>N, <sup>16</sup>O/<sup>18</sup>O, and <sup>12</sup>C/<sup>13</sup>C isotopic substitution in the dissociation of beta-sheet polyglycine dimers of different lengths into two monomer chains. This dissociation reaction, proceeding via breaking of the interchain hydrogen bonds (H-bonds), is considered to be a model of unfolding of the secondary structure of proteins. The calculated strengthening of the interchain hydrogen bonds <inline-formula><math xmlns="http://www.w3.org/1998/Math/MathML" display="inline"><semantics><mrow><mi>N</mi><mo>−</mo><mi>H</mi><mo>⋯</mo><mi>O</mi><mo>=</mo><mi>C</mi></mrow></semantics></math></inline-formula> due to heavy isotope substitution decreases in the row H/D >> <sup>14</sup>N/<sup>15</sup>N > <sup>16</sup>O/<sup>18</sup>O > <sup>12</sup>C/<sup>13</sup>C. The KIE for H/D substitution, defined as the ratio of the rate constants <inline-formula><math xmlns="http://www.w3.org/1998/Math/MathML" display="inline"><semantics><mrow><mstyle scriptlevel="0" displaystyle="true"><mfrac><mrow><mi>k</mi><mo>(</mo><mi>H</mi><mo>)</mo></mrow><mrow><mi>k</mi><mo>(</mo><mi>D</mi><mo>)</mo></mrow></mfrac></mstyle></mrow></semantics></math></inline-formula>, was calculated with the use of a “completely loose” transition state model. The results of the calculations show that a very high H/D isotope effect can be achieved for proteins even with moderately long chains connected by dozens of interchain H-bonds. The results obtained also indicate that the heavy isotope substitution in the internal (interchain) and external H-bonds, located on the periphery of a dimer, can provide comparable effects on secondary structure stabilization. |
| format | Article |
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| institution | Kabale University |
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| spelling | doaj-art-5a6ae7b68212468099cbdb11de6e30482025-01-24T13:25:09ZengMDPI AGBiomolecules2218-273X2025-01-011519210.3390/biom15010092Kinetic Isotope Effect in the Unfolding of a Protein Secondary Structure: Calculations for Beta-Sheet Polyglycine Dimers as a ModelAlexey O. Yanshin0Vitaly G. Kiselev1Alexey V. Baklanov2Institute of Chemical Kinetics and Combustion SB RAS, 3 Institutskaya Street, Novosibirsk 630090, RussiaInstitute of Chemical Kinetics and Combustion SB RAS, 3 Institutskaya Street, Novosibirsk 630090, RussiaInstitute of Chemical Kinetics and Combustion SB RAS, 3 Institutskaya Street, Novosibirsk 630090, RussiaIn the present work, we performed calculations of the kinetic isotope effect (KIE) on H/D, <sup>14</sup>N/<sup>15</sup>N, <sup>16</sup>O/<sup>18</sup>O, and <sup>12</sup>C/<sup>13</sup>C isotopic substitution in the dissociation of beta-sheet polyglycine dimers of different lengths into two monomer chains. This dissociation reaction, proceeding via breaking of the interchain hydrogen bonds (H-bonds), is considered to be a model of unfolding of the secondary structure of proteins. The calculated strengthening of the interchain hydrogen bonds <inline-formula><math xmlns="http://www.w3.org/1998/Math/MathML" display="inline"><semantics><mrow><mi>N</mi><mo>−</mo><mi>H</mi><mo>⋯</mo><mi>O</mi><mo>=</mo><mi>C</mi></mrow></semantics></math></inline-formula> due to heavy isotope substitution decreases in the row H/D >> <sup>14</sup>N/<sup>15</sup>N > <sup>16</sup>O/<sup>18</sup>O > <sup>12</sup>C/<sup>13</sup>C. The KIE for H/D substitution, defined as the ratio of the rate constants <inline-formula><math xmlns="http://www.w3.org/1998/Math/MathML" display="inline"><semantics><mrow><mstyle scriptlevel="0" displaystyle="true"><mfrac><mrow><mi>k</mi><mo>(</mo><mi>H</mi><mo>)</mo></mrow><mrow><mi>k</mi><mo>(</mo><mi>D</mi><mo>)</mo></mrow></mfrac></mstyle></mrow></semantics></math></inline-formula>, was calculated with the use of a “completely loose” transition state model. The results of the calculations show that a very high H/D isotope effect can be achieved for proteins even with moderately long chains connected by dozens of interchain H-bonds. The results obtained also indicate that the heavy isotope substitution in the internal (interchain) and external H-bonds, located on the periphery of a dimer, can provide comparable effects on secondary structure stabilization.https://www.mdpi.com/2218-273X/15/1/92proteinunfoldinghydrogen bondkinetic isotope effectpolyglycine dimercompletely loose transition state |
| spellingShingle | Alexey O. Yanshin Vitaly G. Kiselev Alexey V. Baklanov Kinetic Isotope Effect in the Unfolding of a Protein Secondary Structure: Calculations for Beta-Sheet Polyglycine Dimers as a Model Biomolecules protein unfolding hydrogen bond kinetic isotope effect polyglycine dimer completely loose transition state |
| title | Kinetic Isotope Effect in the Unfolding of a Protein Secondary Structure: Calculations for Beta-Sheet Polyglycine Dimers as a Model |
| title_full | Kinetic Isotope Effect in the Unfolding of a Protein Secondary Structure: Calculations for Beta-Sheet Polyglycine Dimers as a Model |
| title_fullStr | Kinetic Isotope Effect in the Unfolding of a Protein Secondary Structure: Calculations for Beta-Sheet Polyglycine Dimers as a Model |
| title_full_unstemmed | Kinetic Isotope Effect in the Unfolding of a Protein Secondary Structure: Calculations for Beta-Sheet Polyglycine Dimers as a Model |
| title_short | Kinetic Isotope Effect in the Unfolding of a Protein Secondary Structure: Calculations for Beta-Sheet Polyglycine Dimers as a Model |
| title_sort | kinetic isotope effect in the unfolding of a protein secondary structure calculations for beta sheet polyglycine dimers as a model |
| topic | protein unfolding hydrogen bond kinetic isotope effect polyglycine dimer completely loose transition state |
| url | https://www.mdpi.com/2218-273X/15/1/92 |
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