1p8j
From Proteopedia
(New page: 200px<br /><applet load="1p8j" size="450" color="white" frame="true" align="right" spinBox="true" caption="1p8j, resolution 2.60Å" /> '''CRYSTAL STRUCTURE OF...) |
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| - | [[Image:1p8j.gif|left|200px]]<br /><applet load="1p8j" size=" | + | [[Image:1p8j.gif|left|200px]]<br /><applet load="1p8j" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1p8j, resolution 2.60Å" /> | caption="1p8j, resolution 2.60Å" /> | ||
'''CRYSTAL STRUCTURE OF THE PROPROTEIN CONVERTASE FURIN'''<br /> | '''CRYSTAL STRUCTURE OF THE PROPROTEIN CONVERTASE FURIN'''<br /> | ||
==Overview== | ==Overview== | ||
| - | In eukaryotes, many essential secreted proteins and peptide hormones are | + | In eukaryotes, many essential secreted proteins and peptide hormones are excised from larger precursors by members of a class of calcium-dependent endoproteinases, the prohormone-proprotein convertases (PCs). Furin, the best-characterized member of the mammalian PC family, has essential functions in embryogenesis and homeostasis but is also implicated in various pathologies such as tumor metastasis, neurodegeneration and various bacterial and viral diseases caused by such pathogens as anthrax and pathogenic Ebola virus strains. Furin cleaves protein precursors with narrow specificity following basic Arg-Xaa-Lys/Arg-Arg-like motifs. The 2.6 A crystal structure of the decanoyl-Arg-Val-Lys-Arg-chloromethylketone (dec-RVKR-cmk)-inhibited mouse furin ectodomain, the first PC structure, reveals an eight-stranded jelly-roll P domain associated with the catalytic domain. Contoured surface loops shape the active site by cleft, thus explaining furin's stringent requirement for arginine at P1 and P4, and lysine at P2 sites by highly charge-complementary pockets. The structure also explains furin's preference for basic residues at P3, P5 and P6 sites. This structure will aid in the rational design of antiviral and antibacterial drugs. |
==About this Structure== | ==About this Structure== | ||
| - | 1P8J is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus] with NAG, CA and SO4 as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Furin Furin], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.75 3.4.21.75] Full crystallographic information is available from [http:// | + | 1P8J is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus] with <scene name='pdbligand=NAG:'>NAG</scene>, <scene name='pdbligand=CA:'>CA</scene> and <scene name='pdbligand=SO4:'>SO4</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Furin Furin], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.75 3.4.21.75] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1P8J OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Bode, W.]] | [[Category: Bode, W.]] | ||
| - | [[Category: Bourenkov, G | + | [[Category: Bourenkov, G P.]] |
[[Category: Cameron, A.]] | [[Category: Cameron, A.]] | ||
[[Category: Henrich, S.]] | [[Category: Henrich, S.]] | ||
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[[Category: Kiefersauer, R.]] | [[Category: Kiefersauer, R.]] | ||
[[Category: Lindberg, I.]] | [[Category: Lindberg, I.]] | ||
| - | [[Category: Than, M | + | [[Category: Than, M E.]] |
[[Category: CA]] | [[Category: CA]] | ||
[[Category: NAG]] | [[Category: NAG]] | ||
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[[Category: spc1]] | [[Category: spc1]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:26:17 2008'' |
Revision as of 12:26, 21 February 2008
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CRYSTAL STRUCTURE OF THE PROPROTEIN CONVERTASE FURIN
Overview
In eukaryotes, many essential secreted proteins and peptide hormones are excised from larger precursors by members of a class of calcium-dependent endoproteinases, the prohormone-proprotein convertases (PCs). Furin, the best-characterized member of the mammalian PC family, has essential functions in embryogenesis and homeostasis but is also implicated in various pathologies such as tumor metastasis, neurodegeneration and various bacterial and viral diseases caused by such pathogens as anthrax and pathogenic Ebola virus strains. Furin cleaves protein precursors with narrow specificity following basic Arg-Xaa-Lys/Arg-Arg-like motifs. The 2.6 A crystal structure of the decanoyl-Arg-Val-Lys-Arg-chloromethylketone (dec-RVKR-cmk)-inhibited mouse furin ectodomain, the first PC structure, reveals an eight-stranded jelly-roll P domain associated with the catalytic domain. Contoured surface loops shape the active site by cleft, thus explaining furin's stringent requirement for arginine at P1 and P4, and lysine at P2 sites by highly charge-complementary pockets. The structure also explains furin's preference for basic residues at P3, P5 and P6 sites. This structure will aid in the rational design of antiviral and antibacterial drugs.
About this Structure
1P8J is a Single protein structure of sequence from Mus musculus with , and as ligands. Active as Furin, with EC number 3.4.21.75 Full crystallographic information is available from OCA.
Reference
The crystal structure of the proprotein processing proteinase furin explains its stringent specificity., Henrich S, Cameron A, Bourenkov GP, Kiefersauer R, Huber R, Lindberg I, Bode W, Than ME, Nat Struct Biol. 2003 Jul;10(7):520-6. PMID:12794637
Page seeded by OCA on Thu Feb 21 14:26:17 2008
Categories: Furin | Mus musculus | Single protein | Bode, W. | Bourenkov, G P. | Cameron, A. | Henrich, S. | Huber, R. | Kiefersauer, R. | Lindberg, I. | Than, M E. | CA | NAG | SO4 | Chloromethylketone | P-domain | Pace | Prohormone convertase | Spc1
