5HRT

Crystal structure of mouse autotaxin in complex with a DNA aptamer

Summary for 5HRT

• Entry DOI: 10.2210/pdb5hrt/pdb
• Descriptor: Ectonucleotide pyrophosphatase/phosphodiesterase family member 2, GLYCEROL, modified DNA (34-MER), ... (11 entities in total)
• Functional Keywords: phospholipase d, dna aptamer, hydrolase
• Biological source: Mus musculus (Mouse); More
• Total number of polymer chains: 2
• Total formula weight: 109700.63

Authors

Kato, K.,Nishimasu, H.,Morita, J.,Ishitani, R.,Nureki, O. (deposition date: 2016-01-24, release date: 2016-04-06, Last modification date: 2024-11-06)

Primary citation

Kato, K.,Ikeda, H.,Miyakawa, S.,Futakawa, S.,Nonaka, Y.,Fujiwara, M.,Okudaira, S.,Kano, K.,Aoki, J.,Morita, J.,Ishitani, R.,Nishimasu, H.,Nakamura, Y.,Nureki, O.
Structural basis for specific inhibition of Autotaxin by a DNA aptamer
Nat.Struct.Mol.Biol., 23:395-401, 2016

PubMed Abstract: ATX is a plasma lysophospholipase D that hydrolyzes lysophosphatidylcholine (LPC) and produces lysophosphatidic acid. To date, no ATX-inhibition-mediated treatment strategies for human diseases have been established. Here, we report anti-ATX DNA aptamers that inhibit ATX with high specificity and efficacy. We solved the crystal structure of ATX in complex with the anti-ATX aptamer RB011, at 2.0-Å resolution. RB011 binds in the vicinity of the active site through base-specific interactions, thus preventing the access of the choline moiety of LPC substrates. Using the structural information, we developed the modified anti-ATX DNA aptamer RB014, which exhibited in vivo efficacy in a bleomycin-induced pulmonary fibrosis mouse model. Our findings reveal the structural basis for the specific inhibition of ATX by the anti-ATX aptamer and highlight the therapeutic potential of anti-ATX aptamers for the treatment of human diseases, such as pulmonary fibrosis.

PubMed: 27043297
DOI: 10.1038/nsmb.3200

Experimental method

X-RAY DIFFRACTION (1.997 Å)