Biochemistry, Department of

 

Document Type

Article

Date of this Version

2017

Citation

Biochemistry. 2017 January 17; 56(2): 391–402

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Public Access

doi:10.1021/acs.biochem.6b00906

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 homolog 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 Asp23 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 E. coli homolog YajL shows both residues may be protonated at the H-bonded oxygen atoms, potentially consistent with an LBHB. A PDB-wide screen identifies candidate carboxylic acid H-bonds in approximately 14% of proteins, which are typically short (O-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.

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