Short Carboxylic Acid–Carboxylate Hydrogen Bonds Can Have Fully Localized Protons

Lin, Jiusheng; Pozharski, Edwin; Wilson, Mark A.

doi:10.1021/acs.biochem.6b00906

Title: Short Carboxylic Acid–Carboxylate Hydrogen Bonds Can Have Fully Localized Protons

Journal Article · Sun Dec 18 00:00:00 EST 2016 · Biochemistry

DOI:https://doi.org/10.1021/acs.biochem.6b00906· OSTI ID:1339745

Lin, Jiusheng ^[1]; Pozharski, Edwin ^[2];

^[1]

Univ. of Nebraska, Lincoln, NE (United States)
Univ. of Maryland School of Medicine, Baltimore, MD (United States); Inst. for Bioscience and Biotechnology Research, Rockville, MD (United States)

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 [d_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 pK_a. 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. Furthermore, 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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Research Organization:: Argonne National Laboratory (ANL), Argonne, IL (United States)

Sponsoring Organization:: USDOE Office of Science (SC), Basic Energy Sciences (BES). Scientific User Facilities Division; USDOE Office of Science (SC), Biological and Environmental Research (BER); National Inst. of Health; National Inst. of General Medical Sciences (NIGMS)

Grant/Contract Number:: AC02-76SF00515; AC02-06CH11357; P41GM103393; R24GM111072

OSTI ID:: 1339745

Journal Information:: Biochemistry, Vol. 56, Issue 2; ISSN 0006-2960

Publisher:: American Chemical Society (ACS)Copyright Statement

Country of Publication:: United States

Language:: ENGLISH

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Cited by: 31 works

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Title: Short Carboxylic Acid–Carboxylate Hydrogen Bonds Can Have Fully Localized Protons

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