2nwn: Difference between revisions
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[[Image:2nwn.gif|left|200px]] | [[Image:2nwn.gif|left|200px]] | ||
'''New Pharmacophore for Serine Protease Inhibition Revealed by Crystal Structure of Human Urokinase-type Plasminogen Activator Complexed with a Cyclic Peptidyl Inhibitor, upain-1''' | {{Structure | ||
|PDB= 2nwn |SIZE=350|CAPTION= <scene name='initialview01'>2nwn</scene>, resolution 2.15Å | |||
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|LIGAND= | |||
|ACTIVITY= | |||
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'''New Pharmacophore for Serine Protease Inhibition Revealed by Crystal Structure of Human Urokinase-type Plasminogen Activator Complexed with a Cyclic Peptidyl Inhibitor, upain-1''' | |||
==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
2NWN is a [ | 2NWN is a [[Protein complex]] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2NWN OCA]. | ||
==Reference== | ==Reference== | ||
Structural basis of specificity of a peptidyl urokinase inhibitor, upain-1., Zhao G, Yuan C, Wind T, Huang Z, Andreasen PA, Huang M, J Struct Biol. 2007 Oct;160(1):1-10. Epub 2007 Jun 20. PMID:[http:// | Structural basis of specificity of a peptidyl urokinase inhibitor, upain-1., Zhao G, Yuan C, Wind T, Huang Z, Andreasen PA, Huang M, J Struct Biol. 2007 Oct;160(1):1-10. Epub 2007 Jun 20. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/17692534 17692534] | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Protein complex]] | [[Category: Protein complex]] | ||
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[[Category: pharmacophore]] | [[Category: pharmacophore]] | ||
[[Category: sgc]] | [[Category: sgc]] | ||
[[Category: structural | [[Category: structural genomic]] | ||
[[Category: structural genomics consortium]] | [[Category: structural genomics consortium]] | ||
[[Category: urokinase-type plasminogen activator]] | [[Category: urokinase-type plasminogen activator]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 17:52:04 2008'' | ||
Revision as of 18:52, 20 March 2008
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New Pharmacophore for Serine Protease Inhibition Revealed by Crystal Structure of Human Urokinase-type Plasminogen Activator Complexed with a Cyclic Peptidyl Inhibitor, upain-1
OverviewOverview
Urokinase-type plasminogen activator (uPA) plays a crucial role in the regulation of plasminogen activation, tumor cell adhesion and migration. The inhibition of uPA activity is a promising mechanism for anti-cancer therapy. A cyclic peptidyl inhibitor, upain-1, CSWRGLENHRMC, was identified recently as a competitive and highly specific uPA inhibitor. We determined the crystal structure of uPA in complex with upain-1 at 2.15 A. The structure reveals that the cyclic peptide adopts a rigid conformation stabilized by a disulfide bond (residues 1-12) and three tight beta turns (residues 3-6, 6-9, 9-12). The Glu7 residue of upain-1 forms hydrogen bonds with the main chain nitrogen atoms of residues 4, 5, and 6 of upain-1, and is also critical for maintaining the active conformation of upain-1. The Arg4 of upain-1 is inserted into the uPA's specific S1 pocket. The Ser2 residue of upain-1 locates close to the S1beta pocket of uPA. The Gly5 and Glu7 residues of upain-1 occupy the S2 pocket and the oxyanion hole of uPA, respectively. Furthermore, the Asn8 residue of upain-1 binds to the 37- and 60-loops of uPA and renders the specificity of upain-1 for uPA. Based on this structure, a new pharmacophore for the design of highly specific uPA inhibitors was proposed.
About this StructureAbout this Structure
2NWN is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.
ReferenceReference
Structural basis of specificity of a peptidyl urokinase inhibitor, upain-1., Zhao G, Yuan C, Wind T, Huang Z, Andreasen PA, Huang M, J Struct Biol. 2007 Oct;160(1):1-10. Epub 2007 Jun 20. PMID:17692534
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