Crystal structures of the catalytic domain of human stromelysin-1 (MMP-3) and collagenase-3 (MMP-13) with a hydroxamic acid inhibitor SM-25453.
Crystal structures of the catalytic domain of human stromelysin-1 (MMP-3) and collagenase-3 (MMP-13) with a hydroxamic acid inhibitor SM-25453 have been solved at 2.01 and 2.37A resolutions, respectively. The results revealed that the binding modes for this inhibitor to MMP-3 and -13 were quite similar. However, subtle comparative differences were observed at the bottom of S1' pockets, which were occupied with the guanidinomethyl moiety of the inhibitor. A remarkable feature of the inhibitor was the deep penetration of its long aliphatic chain into the S1' pocket and exposure of the guanidinomethyl moiety to the solvent.
Kohno
Tetsuya
T
Drug Research Division, Dainippon Sumitomo Pharma Co., Ltd., 3-1-98 Kasugadenaka, Konohana-ku, Osaka 554-0022, Japan. tetsuya-kono@ds-pharma.co.jp
Hochigai
Hitoshi
H
Yamashita
Eiki
E
Tsukihara
Tomitake
T
Kanaoka
Masaharu
M
D000595:Amino Acid Sequence; D018501:Antirheumatic Agents / Q000737:chemistry* / Q000494:pharmacology; D020134:Catalytic Domain; D017364:Collagenases / Q000737:chemistry* / Q000187:drug effects; D018360:Crystallography, X-Ray; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology; D006801:Humans; D006877:Hydroxamic Acids / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000494:pharmacology; D008239:Lysine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D053509:Matrix Metalloproteinase 13; D019278:Matrix Metalloproteinase 3 / Q000737:chemistry* / Q000187:drug effects; D008969:Molecular Sequence Data; D010003:Osteoarthritis / Q000188:drug therapy / Q000201:enzymology; D011487:Protein Conformation
D018501:Antirheumatic Agents; D004791:Enzyme Inhibitors; D006877:Hydroxamic Acids; C511182:SM 25453; D017364:Collagenases; C507079:MMP13 protein, human; D053509:Matrix Metalloproteinase 13; D019278:Matrix Metalloproteinase 3; D008239:Lysine