1nrs: Difference between revisions
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[[Image:1nrs.gif|left|200px]] | [[Image:1nrs.gif|left|200px]] | ||
'''CRYSTALLOGRAPHIC STRUCTURES OF THROMBIN COMPLEXED WITH THROMBIN RECEPTOR PEPTIDES: EXISTENCE OF EXPECTED AND NOVEL BINDING MODES''' | {{Structure | ||
|PDB= 1nrs |SIZE=350|CAPTION= <scene name='initialview01'>1nrs</scene>, resolution 2.4Å | |||
|SITE= | |||
|LIGAND= <scene name='pdbligand=SO3:SULFITE ION'>SO3</scene> | |||
|ACTIVITY= [http://en.wikipedia.org/wiki/Thrombin Thrombin], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.5 3.4.21.5] | |||
|GENE= | |||
}} | |||
'''CRYSTALLOGRAPHIC STRUCTURES OF THROMBIN COMPLEXED WITH THROMBIN RECEPTOR PEPTIDES: EXISTENCE OF EXPECTED AND NOVEL BINDING MODES''' | |||
==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
1NRS is a [ | 1NRS is a [[Protein complex]] structure of sequences from [http://en.wikipedia.org/wiki/Hirudo_medicinalis Hirudo medicinalis] and [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1NRS OCA]. | ||
==Reference== | ==Reference== | ||
Crystallographic structures of thrombin complexed with thrombin receptor peptides: existence of expected and novel binding modes., Mathews II, Padmanabhan KP, Ganesh V, Tulinsky A, Ishii M, Chen J, Turck CW, Coughlin SR, Fenton JW 2nd, Biochemistry. 1994 Mar 22;33(11):3266-79. PMID:[http:// | Crystallographic structures of thrombin complexed with thrombin receptor peptides: existence of expected and novel binding modes., Mathews II, Padmanabhan KP, Ganesh V, Tulinsky A, Ishii M, Chen J, Turck CW, Coughlin SR, Fenton JW 2nd, Biochemistry. 1994 Mar 22;33(11):3266-79. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/8136362 8136362] | ||
[[Category: Hirudo medicinalis]] | [[Category: Hirudo medicinalis]] | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
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[[Category: serine proteinase/receptor]] | [[Category: serine proteinase/receptor]] | ||
''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 13:00:49 2008'' | ||
Revision as of 14:00, 20 March 2008
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| , resolution 2.4Å | |||||||
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| Ligands: | |||||||
| Activity: | Thrombin, with EC number 3.4.21.5 | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
CRYSTALLOGRAPHIC STRUCTURES OF THROMBIN COMPLEXED WITH THROMBIN RECEPTOR PEPTIDES: EXISTENCE OF EXPECTED AND NOVEL BINDING MODES
OverviewOverview
Many of the vital actions of thrombin on platelets and other cells appear to be mediated by the recently cloned seven-transmembrane-domain thrombin receptor. Thrombin activates this receptor by a novel proteolytic mechanism. The amino-terminal exodomain of the receptor contains the sequence LDPRSFLLRNPNDKYEPF. Structure-activity studies with mutant receptors and receptor peptides suggest that this sequence binds to thrombin at two sites: LDPR with the active center of thrombin and KYEPF with the fibrinogen recognition exosite of thrombin. Thrombin then cleaves the Arg41-Ser42 bond to unmask a new amino terminus, which functions as a tethered peptide ligand binding to as yet undefined sites within the body of the receptor to effect receptor activation. We have determined eight crystal structures of thrombin complexed with receptor-based peptides. Each of the two components of the bidentate docking model was captured in individual cocrystals. In one crystal type, the LDPR sequence docked in the active center of thrombin in a manner analogous to d-PheProArg chloromethyl ketone. In other crystals, the KYEPF sequence bound in the fibrinogen anion binding exosite of thrombin in a manner analogous to the DFEEI sequence of the carboxylate-terminal peptide of hirudin. Strikingly, however, generation of a single crystal that includes both components of the anticipated bidentate binding mode was not achieved, apparently because the peptides have a dominant solution S-like conformation that does not bind in a productive way at the active center. This peptide structure apparently favored a novel alternative mode of receptor peptide-thrombin interaction in which the receptor peptides formed an intermolecular bridge between neighboring thrombin molecules, resulting in an infinite peptide thrombin chain in crystals. In this structure, the KYEPF sequence docked in the expected manner at the exosite of one thrombin molecule, but the LDPR sequence docked in an unusual nonproductive mode with the active center of a neighboring molecule. Mutations that removed important determinants of the S-like receptor peptide structure underlying the bridging mode in the receptor itself did not significantly alter thrombin signaling. Additionally, a comparison of receptor density to the responsiveness of a cell did not support a role for receptor oligomerization in signaling. The physiological role for this unexpected intermolecular binding mode, if any, remains to be identified.(ABSTRACT TRUNCATED AT 400 WORDS)
DiseaseDisease
Known diseases associated with this structure: Dysprothrombinemia OMIM:[176930], Hyperprothrombinemia OMIM:[176930], Hypoprothrombinemia OMIM:[176930]
About this StructureAbout this Structure
1NRS is a Protein complex structure of sequences from Hirudo medicinalis and Homo sapiens. Full crystallographic information is available from OCA.
ReferenceReference
Crystallographic structures of thrombin complexed with thrombin receptor peptides: existence of expected and novel binding modes., Mathews II, Padmanabhan KP, Ganesh V, Tulinsky A, Ishii M, Chen J, Turck CW, Coughlin SR, Fenton JW 2nd, Biochemistry. 1994 Mar 22;33(11):3266-79. PMID:8136362
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