title: Temperature dependence of internal motions of protein side-chain NH3(+) groups: insight into energy barriers for transient breakage of hydrogen bonds.
abstract: Although charged side chains play important roles in protein function, their dynamic properties are not well understood. Nuclear magnetic resonance methods for investigating the dynamics of lysine side-chain NH3(+) groups were established recently. Using this methodology, we have studied the temperature dependence of the internal motions of the lysine side-chain NH3(+) groups that form ion pairs with DNA phosphate groups in the HoxD9 homeodomain-DNA complex. For these NH3(+) groups, we determined order parameters and correlation times for bond rotations and reorientations at 15, 22, 28, and 35 °C. The order parameters were found to be virtually constant in this temperature range. In contrast, the bond-rotation correlation times of the NH3(+) groups were found to depend strongly on temperature. On the basis of transition state theory, the energy barriers for NH3(+) rotations were analyzed and compared to those for CH3 rotations. Enthalpies of activation for NH3(+) rotations were found to be significantly higher than those for CH3 rotations, which can be attributed to the requirement of hydrogen bond breakage. However, entropies of activation substantially reduce the overall free energies of activation for NH3(+) rotations to a level comparable to those for CH3 rotations. This entropic reduction in energy barriers may accelerate molecular processes requiring hydrogen bond breakage and play a kinetically important role in protein function.
authors.affiliation: Department of Biochemistry and Molecular Biology, Sealy Center for Structural Biology and Molecular Biophysics, University of Texas Medical Branch , Galveston, Texas 77555-1068, United States.
authors.forename: Levani
authors.initials: L
authors.lastname: Zandarashvili
authors.forename: Junji
authors.initials: J
authors.lastname: Iwahara
mesh_terms: D000818:Animals; D004247:DNA / Q000378:metabolism*; D018398:Homeodomain Proteins / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D006860:Hydrogen Bonding; D008239:Lysine / Q000737:chemistry / Q000378:metabolism*; D051957:MSX1 Transcription Factor / Q000737:chemistry / Q000378:metabolism; D051379:Mice; D008958:Models, Molecular; D009038:Motion; D009363:Neoplasm Proteins / Q000737:chemistry / Q000378:metabolism*; D019906:Nuclear Magnetic Resonance, Biomolecular; D013696:Temperature; D013816:Thermodynamics
chemical_list: C088822:HOXD9 protein, human; D018398:Homeodomain Proteins; D051957:MSX1 Transcription Factor; C484084:Msx1 protein, mouse; D009363:Neoplasm Proteins; D004247:DNA; D008239:Lysine