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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,more » 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.« less

Authors:
 [1];  [2]; ORCiD logo [1]
  1. Univ. of Nebraska, Lincoln, NE (United States)
  2. Univ. of Maryland School of Medicine, Baltimore, MD (United States); Inst. for Bioscience and Biotechnology Research, Rockville, MD (United States)
Publication Date:
Research Org.:
Argonne National Laboratory (ANL), Argonne, IL (United States)
Sponsoring Org.:
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)
OSTI Identifier:
1339745
Grant/Contract Number:  
AC02-76SF00515; AC02-06CH11357; P41GM103393; R24GM111072
Resource Type:
Journal Article: Accepted Manuscript
Journal Name:
Biochemistry
Additional Journal Information:
Journal Volume: 56; Journal Issue: 2; Journal ID: ISSN 0006-2960
Publisher:
American Chemical Society (ACS)
Country of Publication:
United States
Language:
ENGLISH
Subject:
59 BASIC BIOLOGICAL SCIENCES; 37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY; organic acids; reaction mechanisms; genetics; crystal structure; electron density

Citation Formats

Lin, Jiusheng, Pozharski, Edwin, and Wilson, Mark A. Short Carboxylic Acid–Carboxylate Hydrogen Bonds Can Have Fully Localized Protons. United States: N. p., 2016. Web. doi:10.1021/acs.biochem.6b00906.
Lin, Jiusheng, Pozharski, Edwin, & Wilson, Mark A. Short Carboxylic Acid–Carboxylate Hydrogen Bonds Can Have Fully Localized Protons. United States. https://doi.org/10.1021/acs.biochem.6b00906
Lin, Jiusheng, Pozharski, Edwin, and Wilson, Mark A. 2016. "Short Carboxylic Acid–Carboxylate Hydrogen Bonds Can Have Fully Localized Protons". United States. https://doi.org/10.1021/acs.biochem.6b00906. https://www.osti.gov/servlets/purl/1339745.
@article{osti_1339745,
title = {Short Carboxylic Acid–Carboxylate Hydrogen Bonds Can Have Fully Localized Protons},
author = {Lin, Jiusheng and Pozharski, Edwin and Wilson, Mark A.},
abstractNote = {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. Furthermore, this study demonstrates that bond length analysis of atomic resolution X-ray crystal structures provides a useful experimental test of certain candidate LBHBs.},
doi = {10.1021/acs.biochem.6b00906},
url = {https://www.osti.gov/biblio/1339745}, journal = {Biochemistry},
issn = {0006-2960},
number = 2,
volume = 56,
place = {United States},
year = {Sun Dec 18 00:00:00 EST 2016},
month = {Sun Dec 18 00:00:00 EST 2016}
}

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Cited by: 31 works
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Works referencing / citing this record:

Unraveling the structural and chemical features of biological short hydrogen bonds
journal, January 2019


Symmetry and 1 H NMR chemical shifts of short hydrogen bonds: impact of electronic and nuclear quantum effects
journal, January 2020


Unraveling the structural and chemical features of biological short hydrogen bonds
journal, January 2019