5SY6

Atomic resolution structure of human DJ-1, DTT bound

Summary for 5SY6

• Entry DOI: 10.2210/pdb5sy6/pdb
• Related: 5SY4 5SY9 5SYA
• Descriptor: Protein deglycase DJ-1, 2,3-DIHYDROXY-1,4-DITHIOBUTANE (3 entities in total)
• Functional Keywords: dj-1/pfpi superfamily oxidative stress nucleophile elbow, hydrolase, protein binding
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 1
• Total formula weight: 20353.58

Authors

Wilson, M.A.,Lin, J. (deposition date: 2016-08-10, release date: 2016-12-28, Last modification date: 2024-11-20)

Primary citation

Lin, J.,Pozharski, E.,Wilson, M.A.
Short Carboxylic Acid-Carboxylate Hydrogen Bonds Can Have Fully Localized Protons.
Biochemistry, 56:391-402, 2017

PubMed 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 [⟨d⟩ = 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. 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.

PubMed: 27989121
DOI: 10.1021/acs.biochem.6b00906

Experimental method

X-RAY DIFFRACTION (1.15 Å)