Short carboxylic acid-carboxylate hydrogen bonds can have fully localized protons

Jiusheng Lin, Edwin Pozharski, Mark A. Wilson

Research output: Contribution to journalArticle

4 Citations (Scopus)

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 donoracceptor 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.

Original languageEnglish (US)
Pages (from-to)391-402
Number of pages12
JournalBiochemistry
Volume56
Issue number2
DOIs
StatePublished - Jan 1 2017

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Carboxylic Acids
Protons
Hydrogen
Hydrogen bonds
Bond length
Proteins
Crystal structure
X-Rays
X rays
Protonation
Dimers
Escherichia coli

ASJC Scopus subject areas

  • Biochemistry

Cite this

Short carboxylic acid-carboxylate hydrogen bonds can have fully localized protons. / Lin, Jiusheng; Pozharski, Edwin; Wilson, Mark A.

In: Biochemistry, Vol. 56, No. 2, 01.01.2017, p. 391-402.

Research output: Contribution to journalArticle

Lin, Jiusheng ; Pozharski, Edwin ; Wilson, Mark A. / Short carboxylic acid-carboxylate hydrogen bonds can have fully localized protons. In: Biochemistry. 2017 ; Vol. 56, No. 2. pp. 391-402.
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