4L6C

Crystal structure of human mitochondrial deoxyribonucleotidase in complex with the inhibitor pib-t

4L6C の概要

• エントリーDOI: 10.2210/pdb4l6c/pdb
• 関連するPDBエントリー: 4L6A
• 分子名称: 5'(3')-deoxyribonucleotidase, mitochondrial, MAGNESIUM ION, PHOSPHATE ION, ... (7 entities in total)
• 機能のキーワード: 5'-nucleotidase, mitochondria, protein conformation, sequence homology, had-like, hydrolase, dephosphorylation, phosphorylation, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Mitochondrion: Q9NPB1
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 24695.81

構造登録者

Pachl, P.,Brynda, J.,Rezacova, P. (登録日: 2013-06-12, 公開日: 2014-09-10, 最終更新日: 2024-02-28)

主引用文献

Simak, O.,Pachl, P.,Fabry, M.,Budesinsky, M.,Jandusik, T.,Hnizda, A.,Sklenickova, R.,Petrova, M.,Veverka, V.,Rezacova, P.,Brynda, J.,Rosenberg, I.
Conformationally constrained nucleoside phosphonic acids - potent inhibitors of human mitochondrial and cytosolic 5'(3')-nucleotidases.
Org.Biomol.Chem., 12:7971-7982, 2014

PubMed Abstract: This work describes novel in vitro inhibitors of human mitochondrial (mdN) and cytosolic (cdN) 5'(3')-deoxynucleotidases. We designed a series of derivatives of the lead compound (S)-1-[2-deoxy-3,5-O-(phosphonobenzylidene)-β-d-threo-pentofuranosyl]thymine bearing various substituents in the para position of the benzylidene moiety. Detailed kinetic study revealed that certain para substituents increase the inhibitory potency (iodo derivative; K = 2.71 μM) and some induce a shift in selectivity toward cdN (carboxy derivative, K = 11.60 μM; iodoxy derivative, K = 6.60 μM). Crystal structures of mdN in complex with three of these compounds revealed that various para substituents lead to two alternative inhibitor binding modes within the enzyme active site. Two binding modes were also identified for cdN complexes by heteronuclear NMR spectroscopy.

PubMed: 25178098
DOI: 10.1039/c4ob01332h

実験手法

X-RAY DIFFRACTION (1.8 Å)