3WV2

Crystal structure of the catalytic domain of MMP-13 complexed with N-(3-methoxybenzyl)-4-oxo-3,4-dihydroquinazoline-2-carboxamide

Summary for 3WV2

• Entry DOI: 10.2210/pdb3wv2/pdb
• Related: 3WV1 3WV3
• Descriptor: Collagenase 3, ZINC ION, CALCIUM ION, ... (6 entities in total)
• Functional Keywords: hydrolase, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• Biological source: Homo sapiens (human)
• Cellular location: Secreted, extracellular space, extracellular matrix (Probable): P45452
• Total number of polymer chains: 2
• Total formula weight: 39557.33

Authors

Oki, H.,Tanaka, Y. (deposition date: 2014-05-12, release date: 2014-09-24, Last modification date: 2024-05-29)

Primary citation

Nara, H.,Sato, K.,Naito, T.,Mototani, H.,Oki, H.,Yamamoto, Y.,Kuno, H.,Santou, T.,Kanzaki, N.,Terauchi, J.,Uchikawa, O.,Kori, M.
Thieno[2,3-d]pyrimidine-2-carboxamides bearing a carboxybenzene group at 5-position: highly potent, selective, and orally available MMP-13 inhibitors interacting with the S1′′ binding site.
Bioorg.Med.Chem., 22:5487-5505, 2014

PubMed Abstract: On the basis of X-ray co-crystal structures of matrix metalloproteinase-13 (MMP-13) in complex with its inhibitors, our structure-based drug design (SBDD) strategy was directed to achieving high affinity through optimal protein-ligand interaction with the unique S1″ hydrophobic specificity pocket. This report details the optimization of lead compound 44 to highly potent and selective MMP-13 inhibitors based on fused pyrimidine scaffolds represented by the thienopyrimidin-4-one 26c. Furthermore, we have examined the release of collagen fragments from bovine nasal cartilage in response to a combination of IL-1 and oncostatin M.

PubMed: 25192810
DOI: 10.1016/j.bmc.2014.07.025

Experimental method

X-RAY DIFFRACTION (2.3 Å)