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| - | [[Image:1i73.jpg|left|200px]] | + | {{Seed}} |
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| | {{STRUCTURE_1i73| PDB=1i73 | SCENE= }} | | {{STRUCTURE_1i73| PDB=1i73 | SCENE= }} |
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| - | '''COMPLEX OF PRO-LEU-L-TRP PHOSPHONATE WITH THE CATALITIC DOMAIN OF MATRIX METALLO PROTEINASE-8 (MET80 FORM)'''
| + | ===COMPLEX OF PRO-LEU-L-TRP PHOSPHONATE WITH THE CATALITIC DOMAIN OF MATRIX METALLO PROTEINASE-8 (MET80 FORM)=== |
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| - | ==Overview==
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| - | 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.
| + | The line below this paragraph, {{ABSTRACT_PUBMED_10978185}}, adds the Publication Abstract to the page |
| | + | (as it appears on PubMed at http://www.pubmed.gov), where 10978185 is the PubMed ID number. |
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| | + | {{ABSTRACT_PUBMED_10978185}} |
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| | ==About this Structure== | | ==About this Structure== |
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| | [[Category: Tucker, P A.]] | | [[Category: Tucker, P A.]] |
| | [[Category: Hydrolase]] | | [[Category: Hydrolase]] |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May 2 19:39:09 2008'' | + | |
| | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 1 10:30:54 2008'' |
Revision as of 07:30, 1 July 2008
Template:STRUCTURE 1i73
COMPLEX OF PRO-LEU-L-TRP PHOSPHONATE WITH THE CATALITIC DOMAIN OF MATRIX METALLO PROTEINASE-8 (MET80 FORM)
Template:ABSTRACT PUBMED 10978185
About this Structure
1I73 is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
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
Page seeded by OCA on Tue Jul 1 10:30:54 2008
