1su3
From Proteopedia
(New page: 200px<br /> <applet load="1su3" size="450" color="white" frame="true" align="right" spinBox="true" caption="1su3, resolution 2.20Å" /> '''X-ray structure of ...) |
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caption="1su3, resolution 2.20Å" /> | caption="1su3, resolution 2.20Å" /> | ||
'''X-ray structure of human proMMP-1: New insights into collagenase action'''<br /> | '''X-ray structure of human proMMP-1: New insights into collagenase action'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Vertebrate collagenases, members of the matrix metalloproteinase (MMP) | + | Vertebrate collagenases, members of the matrix metalloproteinase (MMP) family, initiate interstitial fibrillar collagen breakdown. It is essential in many biological processes, and unbalanced collagenolysis is associated with diseases such as arthritis, cancer, atherosclerosis, aneurysm, and fibrosis. These metalloproteinases are secreted from the cell as inactive precursors, procollagenases (proMMPs). To gain insights into the structural basis of their activation mechanisms and collagen binding, we have crystallized recombinant human proMMP-1 and determined its structure to 2.2 A resolution. The catalytic metalloproteinase domain and the C-terminal hemopexin (Hpx) domain show the classical MMP-fold, but the structure has revealed new features in surface loops and domain interaction. The prodomain is formed by a three-helix bundle and gives insight into the stepwise activation mechanism of proMMP-1. The prodomain interacts with the Hpx domain, which affects the position of the Hpx domain relative to the catalytic domain. This interaction results in a "closed" configuration of proMMP-1 in contrast to the "open" configuration observed previously for the structure of active MMP-1. This is the first evidence of mobility of the Hpx domain in relation to the catalytic domain, providing an important clue toward the understanding of the collagenase-collagen interaction and subsequent collagenolysis. |
==Disease== | ==Disease== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 1SU3 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 CA, CL, NA, ZN, SO4 and EPE as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Interstitial_collagenase Interstitial collagenase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.24.7 3.4.24.7] Full crystallographic information is available from [http:// | + | 1SU3 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=CA:'>CA</scene>, <scene name='pdbligand=CL:'>CL</scene>, <scene name='pdbligand=NA:'>NA</scene>, <scene name='pdbligand=ZN:'>ZN</scene>, <scene name='pdbligand=SO4:'>SO4</scene> and <scene name='pdbligand=EPE:'>EPE</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Interstitial_collagenase Interstitial collagenase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.24.7 3.4.24.7] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1SU3 OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Bourenkov, G.]] | [[Category: Bourenkov, G.]] | ||
[[Category: Jozic, D.]] | [[Category: Jozic, D.]] | ||
| - | [[Category: Lim, N | + | [[Category: Lim, N H.]] |
[[Category: Maskos, K.]] | [[Category: Maskos, K.]] | ||
[[Category: Nagase, H.]] | [[Category: Nagase, H.]] | ||
| - | [[Category: SPINE, Structural | + | [[Category: SPINE, Structural Proteomics in Europe.]] |
[[Category: CA]] | [[Category: CA]] | ||
[[Category: CL]] | [[Category: CL]] | ||
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[[Category: structural proteomics in europe]] | [[Category: structural proteomics in europe]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 15:05:11 2008'' |
Revision as of 13:05, 21 February 2008
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X-ray structure of human proMMP-1: New insights into collagenase action
Contents |
Overview
Vertebrate collagenases, members of the matrix metalloproteinase (MMP) family, initiate interstitial fibrillar collagen breakdown. It is essential in many biological processes, and unbalanced collagenolysis is associated with diseases such as arthritis, cancer, atherosclerosis, aneurysm, and fibrosis. These metalloproteinases are secreted from the cell as inactive precursors, procollagenases (proMMPs). To gain insights into the structural basis of their activation mechanisms and collagen binding, we have crystallized recombinant human proMMP-1 and determined its structure to 2.2 A resolution. The catalytic metalloproteinase domain and the C-terminal hemopexin (Hpx) domain show the classical MMP-fold, but the structure has revealed new features in surface loops and domain interaction. The prodomain is formed by a three-helix bundle and gives insight into the stepwise activation mechanism of proMMP-1. The prodomain interacts with the Hpx domain, which affects the position of the Hpx domain relative to the catalytic domain. This interaction results in a "closed" configuration of proMMP-1 in contrast to the "open" configuration observed previously for the structure of active MMP-1. This is the first evidence of mobility of the Hpx domain in relation to the catalytic domain, providing an important clue toward the understanding of the collagenase-collagen interaction and subsequent collagenolysis.
Disease
Known diseases associated with this structure: COPD, rate of decline of lung function in OMIM:[120353]
About this Structure
1SU3 is a Single protein structure of sequence from Homo sapiens with , , , , and as ligands. Active as Interstitial collagenase, with EC number 3.4.24.7 Full crystallographic information is available from OCA.
Reference
X-ray structure of human proMMP-1: new insights into procollagenase activation and collagen binding., Jozic D, Bourenkov G, Lim NH, Visse R, Nagase H, Bode W, Maskos K, J Biol Chem. 2005 Mar 11;280(10):9578-85. Epub 2004 Dec 15. PMID:15611040
Page seeded by OCA on Thu Feb 21 15:05:11 2008
Categories: Homo sapiens | Interstitial collagenase | Single protein | Bode, W. | Bourenkov, G. | Jozic, D. | Lim, N H. | Maskos, K. | Nagase, H. | SPINE, Structural Proteomics in Europe. | CA | CL | EPE | NA | SO4 | ZN | Exocite | Hemopexin domain | Prodomain | Spine | Structural genomics | Structural proteomics in europe
