1yk0
From Proteopedia
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|PDB= 1yk0 |SIZE=350|CAPTION= <scene name='initialview01'>1yk0</scene>, resolution 2.4Å | |PDB= 1yk0 |SIZE=350|CAPTION= <scene name='initialview01'>1yk0</scene>, resolution 2.4Å | ||
|SITE= | |SITE= | ||
| - | |LIGAND= <scene name='pdbligand= | + | |LIGAND= <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene> |
|ACTIVITY= | |ACTIVITY= | ||
|GENE= NPR3, ANPRC ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | |GENE= NPR3, ANPRC ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY=[[1yk1|1YK1]] | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1yk0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1yk0 OCA], [http://www.ebi.ac.uk/pdbsum/1yk0 PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1yk0 RCSB]</span> | ||
}} | }} | ||
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==Overview== | ==Overview== | ||
Cardiovascular homeostasis and blood pressure regulation are reliant, in part, on interactions between natriuretic peptide (NP) hormones and natriuretic peptide receptors (NPR). The C-type NPR (NPR-C) is responsible for clearance of NP hormones from the circulation, and displays a cross-reactivity for all NP hormones (ANP, BNP, and CNP), in contrast to other NPRs, which are more restricted in their specificity. In order to elucidate the structural determinants for the binding specificity and cross-reactivity of NPR-C with NP hormones, we have determined the crystal structures of the complexes of NPR-C with atrial natriuretic peptide (ANP), and with brain natriuretic peptide (BNP). A structural comparison of these complexes, with the previous structure of the NPR-C/CNP complex, reveals that NPR-C uses a conformationally inflexible surface to bind three different, highly flexible, NP ligands. The complex structures support a mechanism of rigid promiscuity rather than conformational plasticity by the receptor. While ANP and BNP appear to adopt similar receptor-bound conformations, the CNP structure diverges, yet shares sets of common receptor contacts with the other ligands. The degenerate versus selective hormone recognition properties of different NPRs appears to derive largely from two cavities on the receptor surfaces, pocket I and pocket II, that serve as anchoring sites for hormone side-chains and modulate receptor selectivity. | Cardiovascular homeostasis and blood pressure regulation are reliant, in part, on interactions between natriuretic peptide (NP) hormones and natriuretic peptide receptors (NPR). The C-type NPR (NPR-C) is responsible for clearance of NP hormones from the circulation, and displays a cross-reactivity for all NP hormones (ANP, BNP, and CNP), in contrast to other NPRs, which are more restricted in their specificity. In order to elucidate the structural determinants for the binding specificity and cross-reactivity of NPR-C with NP hormones, we have determined the crystal structures of the complexes of NPR-C with atrial natriuretic peptide (ANP), and with brain natriuretic peptide (BNP). A structural comparison of these complexes, with the previous structure of the NPR-C/CNP complex, reveals that NPR-C uses a conformationally inflexible surface to bind three different, highly flexible, NP ligands. The complex structures support a mechanism of rigid promiscuity rather than conformational plasticity by the receptor. While ANP and BNP appear to adopt similar receptor-bound conformations, the CNP structure diverges, yet shares sets of common receptor contacts with the other ligands. The degenerate versus selective hormone recognition properties of different NPRs appears to derive largely from two cavities on the receptor surfaces, pocket I and pocket II, that serve as anchoring sites for hormone side-chains and modulate receptor selectivity. | ||
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| - | ==Disease== | ||
| - | Known diseases associated with this structure: Acromesomelic dysplasia, Maroteaux type OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=108961 108961]], Hypertension, salt-resistant (1) OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=108962 108962]] | ||
==About this Structure== | ==About this Structure== | ||
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[[Category: Garcia, K C.]] | [[Category: Garcia, K C.]] | ||
[[Category: He, X.]] | [[Category: He, X.]] | ||
| - | [[Category: CL]] | ||
| - | [[Category: NAG]] | ||
[[Category: allosteric activation]] | [[Category: allosteric activation]] | ||
[[Category: crystal structure]] | [[Category: crystal structure]] | ||
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[[Category: natriuretic peptide receptor]] | [[Category: natriuretic peptide receptor]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 01:10:23 2008'' |
Revision as of 22:10, 30 March 2008
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| , resolution 2.4Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | , | ||||||
| Gene: | NPR3, ANPRC (Homo sapiens) | ||||||
| Related: | 1YK1
| ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
structure of natriuretic peptide receptor-C complexed with atrial natriuretic peptide
Overview
Cardiovascular homeostasis and blood pressure regulation are reliant, in part, on interactions between natriuretic peptide (NP) hormones and natriuretic peptide receptors (NPR). The C-type NPR (NPR-C) is responsible for clearance of NP hormones from the circulation, and displays a cross-reactivity for all NP hormones (ANP, BNP, and CNP), in contrast to other NPRs, which are more restricted in their specificity. In order to elucidate the structural determinants for the binding specificity and cross-reactivity of NPR-C with NP hormones, we have determined the crystal structures of the complexes of NPR-C with atrial natriuretic peptide (ANP), and with brain natriuretic peptide (BNP). A structural comparison of these complexes, with the previous structure of the NPR-C/CNP complex, reveals that NPR-C uses a conformationally inflexible surface to bind three different, highly flexible, NP ligands. The complex structures support a mechanism of rigid promiscuity rather than conformational plasticity by the receptor. While ANP and BNP appear to adopt similar receptor-bound conformations, the CNP structure diverges, yet shares sets of common receptor contacts with the other ligands. The degenerate versus selective hormone recognition properties of different NPRs appears to derive largely from two cavities on the receptor surfaces, pocket I and pocket II, that serve as anchoring sites for hormone side-chains and modulate receptor selectivity.
About this Structure
1YK0 is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Structural determinants of natriuretic peptide receptor specificity and degeneracy., He XL, Dukkipati A, Garcia KC, J Mol Biol. 2006 Aug 25;361(4):698-714. Epub 2006 Jul 10. PMID:16870210
Page seeded by OCA on Mon Mar 31 01:10:23 2008
