1V7A

Crystal structures of adenosine deaminase complexed with potent inhibitors

Summary for 1V7A

• Entry DOI: 10.2210/pdb1v7a/pdb
• Related: 1V78 1V79
• Descriptor: adenosine deaminase, ZINC ION, 1-{(1R,2S)-2-HYDROXY-1-[2-(2-NAPHTHYLOXY)ETHYL]PROPYL}-1H-IMIDAZONE-4-CARBOXAMIDE, ... (4 entities in total)
• Functional Keywords: beta barrel, zinc, hydrolase
• Biological source: Bos taurus (cattle)
• Cellular location: Cell membrane; Peripheral membrane protein; Extracellular side (By similarity): P56658
• Total number of polymer chains: 1
• Total formula weight: 40746.47

Authors

Kinoshita, T. (deposition date: 2003-12-14, release date: 2004-12-21, Last modification date: 2023-12-27)

Primary citation

Terasaka, T.,Okumura, H.,Tsuji, K.,Kato, T.,Nakanishi, I.,Kinoshita, T.,Kato, Y.,Kuno, M.,Seki, N.,Naoe, Y.,Inoue, T.,Tanaka, K.,Nakamura, K.
Structure-based design and synthesis of non-nucleoside, potent, and orally bioavailable adenosine deaminase inhibitors
J.Med.Chem., 47:2728-2731, 2004

PubMed Abstract: We disclose optimization efforts based on the novel non-nucleoside adenosine deaminase (ADA) inhibitor, 4 (K(i) = 680 nM). Structure-based drug design utilizing the crystal structure of the 4/ADA complex led to discovery of 5 (K(i) = 11 nM, BA = 30% in rats). Furthermore, from metabolic considerations, we discovered two inhibitors with improved oral bioavailability [6 (K(i) = 13 nM, BA = 44%) and 7 (K(i) = 9.8 nM, BA = 42%)]. 6 demonstrated in vivo efficacy in models of inflammation and lymphoma.

PubMed: 15139750
DOI: 10.1021/jm0499559

Experimental method

X-RAY DIFFRACTION (2.5 Å)