title: Unconventional N-H…N Hydrogen Bonds Involving Proline Backbone Nitrogen in Protein Structures.
abstract: Contrary to DNA double-helical structures, hydrogen bonds (H-bonds) involving nitrogen as the acceptor are not common in protein structures. We systematically searched N-H…N H-bonds in two different sets of protein structures. Data set I consists of neutron diffraction and ultrahigh-resolution x-ray structures (0.9 Å resolution or better) and the hydrogen atom positions in these structures were determined experimentally. Data set II contains structures determined using x-ray diffraction (resolution ≤ 1.8 Å) and the positions of hydrogen atoms were generated using a computational method. We identified 114 and 14,347 potential N-H…N H-bonds from these two data sets, respectively, and 56-66% of these were of the Ni+1-Hi+1…Ni type, with Ni being the proline backbone nitrogen. To further understand the nature of such unusual contacts, we performed quantum chemical calculations on the model compound N-acetyl-L-proline-N-methylamide (Ace-Pro-NMe) with coordinates taken from the experimentally determined structures. A potential energy profile generated by varying the ψ dihedral angle in Ace-Pro-NMe indicates that the conformation with the N-H…N H-bond is the most stable. An analysis of H-bond-forming proline residues reveals that more than 30% of the proline carbonyl groups are also involved in n → π(∗) interactions with the carbonyl carbon of the preceding residue. Natural bond orbital analyses demonstrate that the strength of N-H…N H-bonds is less than half of that observed for a conventional H-bond. This study clearly establishes the H-bonding capability of proline nitrogen and its prevalence in protein structures. We found many proteins with multiple instances of H-bond-forming prolines. With more than 15% of all proline residues participating in N-H…N H-bonds, we suggest a new, to our knowledge, structural role for proline in providing stability to loops and capping regions of secondary structures in proteins.
authors.affiliation: Department of Biological Sciences and Bioengineering, Indian Institute of Technology Kanpur, Kanpur, India.
authors.forename: R N V Krishna
authors.initials: RN
authors.lastname: Deepak
authors.affiliation: Department of Biological Sciences and Bioengineering, Indian Institute of Technology Kanpur, Kanpur, India. Electronic address: rsankar@iitk.ac.in.
authors.forename: Ramasubbu
authors.initials: R
authors.lastname: Sankararamakrishnan
mesh_terms: D006860:Hydrogen Bonding; D008958:Models, Molecular; D009584:Nitrogen / Q000737:chemistry*; D011392:Proline / Q000737:chemistry*; D017433:Protein Structure, Secondary; D011506:Proteins / Q000737:chemistry*; D011789:Quantum Theory
chemical_list: D011506:Proteins; D011392:Proline; D009584:Nitrogen