1d8f
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CRYSTAL STRUCTURE OF MMP3 COMPLEXED WITH A PIPERAZINE BASED INHIBITOR.
OverviewOverview
A new generation of cyclic matrix metalloproteinase (MMP) inhibitors, derived from dl-piperazinecarboxylic acid has been described. The design, involves: incorporation of hydroxamic acid as the bidentate chelating, agent for catalytic Zn(2+), placement of a sulfonamide group at the, 1N-position of the piperazine ring to fill the S1' pocket of the enzyme, and finally attachment of diverse functional groups at the 4N-position to, optimize potency and peroral absorption. A unique combination of all three, elements produced inhibitor 20 with high affinity for MMPs 1, 3, 9, and 13, (24, 18, 1.9, and 1.3 nM, respectively). X-ray crystallography data, obtained for MMP-3 cocrystallized with 20 gave detailed information on key, binding interactions defining an overall scaffold geometry for, piperazine-based MMP inhibitors.
DiseaseDisease
Known diseases associated with this structure: Coronary heart disease, susceptibility to OMIM:[185250]
About this StructureAbout this Structure
1D8F is a Single protein structure of sequence from Homo sapiens with ZN, CA and SPI as ligands. Active as Stromelysin 1, with EC number 3.4.24.17 Full crystallographic information is available from OCA.
ReferenceReference
Design and synthesis of piperazine-based matrix metalloproteinase inhibitors., Cheng M, De B, Pikul S, Almstead NG, Natchus MG, Anastasio MV, McPhail SJ, Snider CE, Taiwo YO, Chen L, Dunaway CM, Gu F, Dowty ME, Mieling GE, Janusz MJ, Wang-Weigand S, J Med Chem. 2000 Feb 10;43(3):369-80. PMID:10669564
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