3N2U

Crystal structure of the catalytic domain of human MMP12 complexed with the inhibitor N-hydroxy-2-(4-methoxy-N(2-(3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yloxy)ethyl)phenylsulfonamido)acetamide

Summary for 3N2U

• Entry DOI: 10.2210/pdb3n2u/pdb
• Related: 3F15 3F16 3F17 3N2V
• Descriptor: Macrophage metalloelastase, ZINC ION, CALCIUM ION, ... (5 entities in total)
• Functional Keywords: matrix metalloproteinase, mmp12, elastase, complex (elastase-inhibitor), metallo elastase, extracellular matrix, glycoprotein, hydrolase, metal-inding, metalloprotease, protease, secreted, zymogen, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• Biological source: Homo sapiens (human)
• Cellular location: Secreted, extracellular space, extracellular matrix : P39900
• Total number of polymer chains: 1
• Total formula weight: 18201.99

Authors

Calderone, V. (deposition date: 2010-05-19, release date: 2010-11-10, Last modification date: 2023-09-06)

Primary citation

Attolino, E.,Calderone, V.,Dragoni, E.,Fragai, M.,Richichi, B.,Luchinat, C.,Nativi, C.
Structure-based approach to nanomolar, water soluble matrix metalloproteinases inhibitors (MMPIs).
Eur.J.Med.Chem., 45:5919-5925, 2010

PubMed Abstract: N-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.

PubMed: 20965620
DOI: 10.1016/j.ejmech.2010.09.057

Experimental method

X-RAY DIFFRACTION (1.81 Å)