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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| Main Authors: | , , |
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| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2025-01-01
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| Series: | Biomolecules |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2218-273X/15/1/92 |
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| Summary: | 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. |
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| ISSN: | 2218-273X |