1itv
From Proteopedia
(New page: 200px<br /> <applet load="1itv" size="450" color="white" frame="true" align="right" spinBox="true" caption="1itv, resolution 1.95Å" /> '''Dimeric form of the...) |
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| - | [[Image:1itv.gif|left|200px]]<br /> | + | [[Image:1itv.gif|left|200px]]<br /><applet load="1itv" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="1itv" size=" | + | |
caption="1itv, resolution 1.95Å" /> | caption="1itv, resolution 1.95Å" /> | ||
'''Dimeric form of the haemopexin domain of MMP9'''<br /> | '''Dimeric form of the haemopexin domain of MMP9'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Matrix metalloproteinase (MMPs) are critical for the degradation of | + | Matrix metalloproteinase (MMPs) are critical for the degradation of extracellular matrix components and, therefore, need to be regulated tightly. Almost all MMPs share a homologous C-terminal haemopexin-like domain (PEX). Besides its role in macromolecular substrate processing, the PEX domains appear to play a major role in regulating MMP activation, localisation and inhibition. One intriguing property of MMP9 is its competence to bind different proteins, involved in these regulatory processes, with high affinity at an overlapping recognition site on its PEX domain. With the crystal structure of the PEX9 dimer, we present the first example of how PEX domains accomplish these diverse roles. Blade IV of PEX9 mediates the non-covalent and predominantly hydrophobic dimerisation contact. Large shifts of blade III and, in particular, blade IV, accompany the dimerisation, resulting in a remarkably asymmetric homodimeric structure. The asymmetry provides a novel mechanism of adaptive protein recognition, where different proteins (PEX9, PEX1, and TIMP1) can bind with high affinity to PEX9 at an overlapping site. Finally, the structure illustrates how the dimerisation generates new properties on both a physico-chemical and functional level. |
==About this Structure== | ==About this Structure== | ||
| - | 1ITV is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with SO4 as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/Gelatinase_B Gelatinase B], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.24.35 3.4.24.35] Full crystallographic information is available from [http:// | + | 1ITV is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=SO4:'>SO4</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/Gelatinase_B Gelatinase B], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.24.35 3.4.24.35] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1ITV OCA]. |
==Reference== | ==Reference== | ||
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[[Category: mmp9]] | [[Category: mmp9]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:15:37 2008'' |
Revision as of 11:15, 21 February 2008
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Dimeric form of the haemopexin domain of MMP9
Overview
Matrix metalloproteinase (MMPs) are critical for the degradation of extracellular matrix components and, therefore, need to be regulated tightly. Almost all MMPs share a homologous C-terminal haemopexin-like domain (PEX). Besides its role in macromolecular substrate processing, the PEX domains appear to play a major role in regulating MMP activation, localisation and inhibition. One intriguing property of MMP9 is its competence to bind different proteins, involved in these regulatory processes, with high affinity at an overlapping recognition site on its PEX domain. With the crystal structure of the PEX9 dimer, we present the first example of how PEX domains accomplish these diverse roles. Blade IV of PEX9 mediates the non-covalent and predominantly hydrophobic dimerisation contact. Large shifts of blade III and, in particular, blade IV, accompany the dimerisation, resulting in a remarkably asymmetric homodimeric structure. The asymmetry provides a novel mechanism of adaptive protein recognition, where different proteins (PEX9, PEX1, and TIMP1) can bind with high affinity to PEX9 at an overlapping site. Finally, the structure illustrates how the dimerisation generates new properties on both a physico-chemical and functional level.
About this Structure
1ITV is a Single protein structure of sequence from Homo sapiens with as ligand. Active as Gelatinase B, with EC number 3.4.24.35 Full crystallographic information is available from OCA.
Reference
Structural basis of the adaptive molecular recognition by MMP9., Cha H, Kopetzki E, Huber R, Lanzendorfer M, Brandstetter H, J Mol Biol. 2002 Jul 26;320(5):1065-79. PMID:12126625
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