1i76 | pdb_00001i76

COMPLEX OF 2-(BIPHENYL-4-SULFONYL)-1,2,3,4-TETRAHYDRO-ISOQUINOLINE-3-CARBOXYLIC ACID (D-TIC DERIVATIVE) WITH T CATALITIC DOMAIN OF MATRIX METALLO PROTEINASE-8 (MET80 FORM)

spinqualitylabelsall models 1i76, resolution 1.20Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 1i76 is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.2Å Ligands: BSI, CA, ZN Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function MMP8_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 PubMed Two crystal structures of human neutrophil collagenase (HNC, MMP-8), one complexed with a primed- and the other with an unprimed-side inhibitor, were determined using synchrotron radiation at 100 K. Both inhibitors contain non-hydroxamate zinc-binding functions. The Pro-Leu-L-Trp(P)(OH)(2) occupies the unprimed region of the active site, furnishes new structural information regarding interaction between the catalytic zinc ion and the phosphonate group, and is the only example of occupation of the S(1) subsite of MMP-8 by the bulky tryptophan side chain. The (R)-2-(biphenyl-4-ylsulfonyl)-1,2,3, 4-tetrahydroisochinolin-3-carboxylic acid, a conformationally constrained D-Tic derivative, accommodates its biphenyl substituent into the deep primary specificity S(1)' subsite, inducing a widening of the entrance to this pocket; this modification of the protein, mainly consisting in a shift of the segment centered at Pro217, is observed for the first time in MMP-8 complexes. Cation-aromatic interactions can stabilize the formation of both complexes, and the beneficial effect of aromatic substituents in proximity of the catalytic zinc ion is discussed. The phosphonate group bound to either a primed- or unprimed-side inhibitor maintains the same relative position with respect to the catalytic zinc ion, suggesting that this binding function can be exploited for the design of combined inhibitors assembled to interact with both primed and unprimed regions of the active cleft. Two crystal structures of human neutrophil collagenase, one complexed with a primed- and the other with an unprimed-side inhibitor: implications for drug design.,Gavuzzo E, Pochetti G, Mazza F, Gallina C, Gorini B, D'Alessio S, Pieper M, Tschesche H, Tucker PA J Med Chem. 2000 Sep 7;43(18):3377-85. PMID:10978185 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Matrix metalloproteinase 3D structures

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