title: Helix-Capping Histidines: Diversity of N-H···N Hydrogen Bond Strength Revealed by (2h)JNN Scalar Couplings.
abstract: In addition to its well-known roles as an electrophile and general acid, the side chain of histidine often serves as a hydrogen bond (H-bond) acceptor. These H-bonds provide a convenient pH-dependent switch for local structure and functional motifs. In hundreds of instances, a histidine caps the N-terminus of α- and 310-helices by forming a backbone NH···Nδ1 H-bond. To characterize the resilience and dynamics of the histidine cap, we measured the trans H-bond scalar coupling constant, (2h)JNN, in several forms of Group 1 truncated hemoglobins and cytochrome b5. The set of 19 measured (2h)JNN values were between 4.0 and 5.4 Hz, generally smaller than in nucleic acids (~6-10 Hz) and indicative of longer, weaker bonds in the studied proteins. A positive linear correlation between (2h)JNN and the difference in imidazole ring (15)N chemical shift (Δ(15)N = |δ(15)Nδ1 - δ(15)Nε2|) was found to be consistent with variable H-bond length and variable cap population related to the ionization of histidine in the capping and noncapping states. The relative ease of (2h)JNN detection suggests that this parameter can become part of the standard arsenal for describing histidines in helix caps and other key structural and catalytic elements involving NH···N H-bonds. The combined nucleic acid and protein data extend the utility of (2h)JNN as a sensitive marker of local structural, dynamic, and thermodynamic properties in biomolecules.
authors.affiliation: T. C. Jenkins Department of Biophysics, Johns Hopkins University , Baltimore, Maryland 21218, United States.
authors.forename: Matthew R
authors.initials: MR
authors.lastname: Preimesberger
authors.affiliation: Biomolecular NMR Center, Johns Hopkins University , Baltimore, Maryland 21218, United States.
authors.forename: Ananya
authors.initials: A
authors.lastname: Majumdar
authors.affiliation: T. C. Jenkins Department of Biophysics, Johns Hopkins University , Baltimore, Maryland 21218, United States.
authors.forename: Selena L
authors.initials: SL
authors.lastname: Rice
authors.affiliation: T. C. Jenkins Department of Biophysics, Johns Hopkins University , Baltimore, Maryland 21218, United States.
authors.forename: Lauren
authors.initials: L
authors.lastname: Que
authors.affiliation: T. C. Jenkins Department of Biophysics, Johns Hopkins University , Baltimore, Maryland 21218, United States.
authors.forename: Juliette T J
authors.initials: JT
authors.lastname: Lecomte
mesh_terms: D001426:Bacterial Proteins / Q000737:chemistry; D002696:Chlamydomonas / Q000737:chemistry; D015786:Cytochromes b5 / Q000737:chemistry; D006418:Heme / Q000737:chemistry; D006454:Hemoglobins / Q000737:chemistry; D006639:Histidine / Q000737:chemistry*; D006860:Hydrogen Bonding; D008706:Methemoglobin / Q000031:analogs & derivatives / Q000737:chemistry; D008958:Models, Molecular; D019906:Nuclear Magnetic Resonance, Biomolecular; D017433:Protein Structure, Secondary; D011506:Proteins / Q000737:chemistry*; D011994:Recombinant Proteins / Q000737:chemistry; D046940:Synechococcus / Q000737:chemistry; D046939:Synechocystis / Q000737:chemistry; D054793:Truncated Hemoglobins / Q000737:chemistry*
chemical_list: D001426:Bacterial Proteins; C102539:GlbN protein, bacteria; D006454:Hemoglobins; D011506:Proteins; D011994:Recombinant Proteins; D054793:Truncated Hemoglobins; C007169:cyanomethemoglobin; C407880:slr2097 protein, Synechocystis; D006418:Heme; D006639:Histidine; D008706:Methemoglobin; D015786:Cytochromes b5