3n2v
Crystal structure of the catalytic domain of human MMP12 complexed with the inhibitor N-hydroxy-2-(N-hydroxyethyl)biphenyl-4-ylsulfonamido)acetamideCrystal structure of the catalytic domain of human MMP12 complexed with the inhibitor N-hydroxy-2-(N-hydroxyethyl)biphenyl-4-ylsulfonamido)acetamide
Structural highlights
FunctionMMP12_HUMAN May be involved in tissue injury and remodeling. Has significant elastolytic activity. Can accept large and small amino acids at the P1' site, but has a preference for leucine. Aromatic or hydrophobic residues are preferred at the P1 site, with small hydrophobic residues (preferably alanine) occupying P3. Publication Abstract from PubMedN-Arylsulfonyl-based MMPs inhibitors (MMPIs) are among the most prominent inhibitors possessing nanomolar affinity. However, their poor bioavailability remains critical for the drug development of this family of molecules. The structural analysis of the complex of NNGH (the most representative member of the family) with MMP-12 provided us with the basis to effectively design simple NNGH analogues with enhanced solubility in water. Following this approach, the sec-butyl residue, not directly involved in the binding with MMP, has been replaced with hydrophilic residues thus yielding new potent inhibitors soluble in water. Structure-based approach to nanomolar, water soluble matrix metalloproteinases inhibitors (MMPIs).,Attolino E, Calderone V, Dragoni E, Fragai M, Richichi B, Luchinat C, Nativi C Eur J Med Chem. 2010 Oct 19. PMID:20965620[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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