title: Short Carboxylic Acid-Carboxylate Hydrogen Bonds Can Have Fully Localized Protons.
abstract: Short hydrogen bonds (H-bonds) have been proposed to play key functional roles in several proteins. The location of the proton in short H-bonds is of central importance, as proton delocalization is a defining feature of low-barrier hydrogen bonds (LBHBs). Experimentally determining proton location in H-bonds is challenging. Here, bond length analysis of atomic (1.15-0.98 Å) resolution X-ray crystal structures of the human protein DJ-1 and its bacterial homologue, YajL, was used to determine the protonation states of H-bonded carboxylic acids. DJ-1 contains a buried, dimer-spanning 2.49 Å H-bond between Glu15 and Asp24 that satisfies standard donor-acceptor distance criteria for a LBHB. Bond length analysis indicates that the proton is localized on Asp24, excluding a LBHB at this location. However, similar analysis of the Escherichia coli homologue YajL shows both residues may be protonated at the H-bonded oxygen atoms, potentially consistent with a LBHB. A Protein Data Bank-wide screen identifies candidate carboxylic acid H-bonds in approximately 14% of proteins, which are typically short [⟨dO-O⟩ = 2.542(2) Å]. Chemically similar H-bonds between hydroxylated residues (Ser/Thr/Tyr) and carboxylates show a trend of lengthening O-O distance with increasing H-bond donor pKa. This trend suggests that conventional electronic effects provide an adequate explanation for short, charge-assisted carboxylic acid-carboxylate H-bonds in proteins, without the need to invoke LBHBs in general. This study demonstrates that bond length analysis of atomic resolution X-ray crystal structures provides a useful experimental test of certain candidate LBHBs.
authors.affiliation: Department of Biochemistry and Redox Biology Center, University of Nebraska , Lincoln, Nebraska 68588, United States.
authors.forename: Jiusheng
authors.initials: J
authors.lastname: Lin
authors.affiliation: Department of Biochemistry and Molecular Biology, Center for Biomolecular Therapeutics, University of Maryland School of Medicine , Baltimore, Maryland 21201, United States.|Institute for Bioscience and Biotechnology Research , Rockville, Maryland 20850, United States.
authors.forename: Edwin
authors.initials: E
authors.lastname: Pozharski
authors.affiliation: Department of Biochemistry and Redox Biology Center, University of Nebraska , Lincoln, Nebraska 68588, United States.
authors.forename: Mark A
authors.identifier: http://orcid.org/0000-0001-6317-900X
authors.initials: MA
authors.lastname: Wilson
mesh_terms: D001224:Aspartic Acid / Q000737:chemistry* / Q000378:metabolism; D002264:Carboxylic Acids / Q000737:chemistry* / Q000378:metabolism; D003001:Cloning, Molecular; D018360:Crystallography, X-Ray; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D029968:Escherichia coli Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D018698:Glutamic Acid / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D006860:Hydrogen Bonding; D006900:Hydroxylation; D008958:Models, Molecular; D000071617:Protein Deglycase DJ-1 / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D000072417:Protein Domains; D011499:Protein Processing, Post-Translational; D017433:Protein Structure, Secondary; D011522:Protons; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D012269:Ribosomal Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism
chemical_list: D002264:Carboxylic Acids; D029968:Escherichia coli Proteins; D011522:Protons; D011994:Recombinant Proteins; D012269:Ribosomal Proteins; C554198:YajL protein, E coli; D001224:Aspartic Acid; D018698:Glutamic Acid; C105131:PARK7 protein, human; D000071617:Protein Deglycase DJ-1