5SYA

Atomic resolution structure of D24N mutant human DJ-1

5SYA の概要

• エントリーDOI: 10.2210/pdb5sya/pdb
• 関連するPDBエントリー: 5SY4 5SY6 5SY9
• 分子名称: Protein deglycase DJ-1, 1,2-ETHANEDIOL (3 entities in total)
• 機能のキーワード: dj-1/pfpi superfamily oxidative stress nucleophile elbow, protein binding
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 20354.48

構造登録者

Wilson, M.A.,Lin, J. (登録日: 2016-08-10, 公開日: 2016-12-28, 最終更新日: 2024-11-13)

主引用文献

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

実験手法

X-RAY DIFFRACTION (1.1 Å)