9YZW

Joint Xray/Neutron structure of Escherichia coli YajL at room temperature

Summary for 9YZW

• Entry DOI: 10.2210/pdb9yzw/pdb
• Descriptor: Chaperone YajL, deuterium(1+) (3 entities in total)
• Functional Keywords: hydrolase, dj-1 superfamily, cysteine dependent enzyme
• Biological source: Escherichia coli
• Total number of polymer chains: 2
• Total formula weight: 42164.66

Authors

Lin, J.,Kovalevsky, A.,Walker, A.R.,Wilson, M.A. (deposition date: 2025-10-30, release date: 2025-11-19, Last modification date: 2026-02-18)

Primary citation

Lin, J.,Gerlits, O.,Kneller, D.W.,Weiss, K.L.,Coates, L.,Clarke, J.L.,Hix, M.A.,Effah, S.Y.,Kovalevsky, A.,Walker, A.R.,Wilson, M.A.
Environmental Contributions to Proton Sharing in Protein Low-Barrier Hydrogen Bonds.
Biochemistry, 2026

PubMed Abstract: Hydrogen bonds (H-bonds) are central to biomolecular structure and dynamics. Although H-bonds are typically characterized by well-defined proton positions, proton delocalization has been proposed to play a role in facilitating enzyme catalysis and allostery in some systems. Experimentally locating protons is difficult, hampering the study of proton mobility in H-bonds. We used neutron crystallography, atomic resolution X-ray bond length analysis, and large quantum mechanics/molecular mechanics-Born-Oppenheimer molecular dynamics (QM/MM-BOMD) simulations to comprehensively characterize the shared proton/deuteron in a Glu-Asp low-barrier hydrogen bond (LBHB) in the bacterial protein YajL that is a conventional H-bond in the homologous disease-associated human protein DJ-1. X-ray bond length analysis of protiated and perdeuterated DJ-1 and YajL shows no significant effect of deuteron substitution on these carboxylic acid-carboxylate H-bonds but does reveal an effect at the active site glutamic acid near a cysteine thiolate. Residues in an H-bonded network that might favor LBHB formation in YajL were interrogated by the mutation of homologous residues in DJ-1. A distal DJ-1 substitution increases proton delocalization in the Glu-Asp H-bond, demonstrating that mutations within extended H-bond networks can modulate proton transfer barriers in carboxylic acid-carboxylate H-bonds. In addition, proton mobility in the H-bond is correlated with dimer-spanning motions in the QM/MM-BOMD simulations of YajL and DJ-1. Our results show that proton delocalization can be tuned using combined bioinformatic, structural, and computational information, opening the possibility of using engineered proton delocalization as a probe of H-bonding environments and as a tool to test hypotheses about LBHB function.

PubMed: 41656622
DOI: 10.1021/acs.biochem.5c00762

Experimental method

NEUTRON DIFFRACTION (1.79 Å)
X-RAY DIFFRACTION (1.65 Å)