3dpf
Crystal structure of the complex between MMP-8 and a non-zinc chelating inhibitorCrystal structure of the complex between MMP-8 and a non-zinc chelating inhibitor
Structural highlights
FunctionMMP8_HUMAN Can degrade fibrillar type I, II, and III collagens. Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedThe mode of binding and the activity of the first two non-zinc chelating, potent, and selective inhibitors of human neutrophil collagenase are reported. The crystal structures of the catalytic domain of MMP-8, respectively complexed with each inhibitor, reveals that both ligands are deeply inserted into the primary specificity subsite S(1)', where they induce a similar conformational change of the surrounding loop that is endowed with the main specificity determinants of MMPs. Accord to this rearrangement, both inhibitors remove the floor of the pocket formed by the Y227 side-chain, rendering available an extra binding region never explored before. The present data show that potent and more selective inhibitors can be obtained by developing ligands able to interact with the selectivity regions of the enzyme rather than with the catalytic zinc ion, which is the common feature of all MMP members. Extra Binding Region Induced by Non-Zinc Chelating Inhibitors into the S(1)' Subsite of Matrix Metalloproteinase 8 (MMP-8) (dagger).,Pochetti G, Montanari R, Gege C, Chevrier C, Taveras AG, Mazza F J Med Chem. 2009 Jan 27. PMID:19173605[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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