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6j21

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Revision as of 09:58, 22 November 2023

Crystal structure of the human NK1 substance P receptor

Structural highlights

6j21 is a 1 chain structure with sequence from Escherichia virus T4 and Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 3.2Å
Ligands:	,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

NK1R_HUMAN This is a receptor for the tachykinin neuropeptide substance P. It is probably associated with G proteins that activate a phosphatidylinositol-calcium second messenger system. The rank order of affinity of this receptor to tachykinins is: substance P > substance K > neuromedin-K.ENLYS_BPT4 Endolysin with lysozyme activity that degrades host peptidoglycans and participates with the holin and spanin proteins in the sequential events which lead to the programmed host cell lysis releasing the mature viral particles. Once the holin has permeabilized the host cell membrane, the endolysin can reach the periplasm and break down the peptidoglycan layer.^[1]

Publication Abstract from PubMed

Neurokinin 1 receptor (NK1R) has key regulating functions in the central and peripheral nervous systems, and NK1R antagonists such as aprepitant have been approved for treating chemotherapy-induced nausea and vomiting. However, the lack of data on NK1R structure and biochemistry has limited further drug development targeting this receptor. Here, we combine NMR spectroscopy and X-ray crystallography to provide dynamic and static characterisation of the binding mode of aprepitant in complexes with human NK1R variants. (19)F-NMR showed a slow off-rate in the binding site, where aprepitant occupies multiple substates that exchange with frequencies in the millisecond range. The environment of the bound ligand is affected by the amino acid in position 2.50, which plays a key role in ligand binding and receptor signaling in class A GPCRs. Crystal structures now reveal how receptor signaling relates to the conformation of the conserved NP(7.50)xxY motif in transmembrane helix VII.

Human substance P receptor binding mode of the antagonist drug aprepitant by NMR and crystallography.,Chen S, Lu M, Liu D, Yang L, Yi C, Ma L, Zhang H, Liu Q, Frimurer TM, Wang MW, Schwartz TW, Stevens RC, Wu B, Wuthrich K, Zhao Q Nat Commun. 2019 Feb 7;10(1):638. doi: 10.1038/s41467-019-08568-5. PMID:30733446^[2]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Moussa SH, Kuznetsov V, Tran TA, Sacchettini JC, Young R. Protein determinants of phage T4 lysis inhibition. Protein Sci. 2012 Apr;21(4):571-82. doi: 10.1002/pro.2042. Epub 2012 Mar 2. PMID:22389108 doi:http://dx.doi.org/10.1002/pro.2042
↑ Chen S, Lu M, Liu D, Yang L, Yi C, Ma L, Zhang H, Liu Q, Frimurer TM, Wang MW, Schwartz TW, Stevens RC, Wu B, Wuthrich K, Zhao Q. Human substance P receptor binding mode of the antagonist drug aprepitant by NMR and crystallography. Nat Commun. 2019 Feb 7;10(1):638. doi: 10.1038/s41467-019-08568-5. PMID:30733446 doi:http://dx.doi.org/10.1038/s41467-019-08568-5

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/6j21"

@@ Line 1: / Line 1: @@
 ==Crystal structure of the human NK1 substance P receptor==
-<StructureSection load='6j21' size='340' side='right'  caption='[[6j21]], [[Resolution|resolution]] 3.20&Aring;' scene=''>
+<StructureSection load='6j21' size='340' side='right'caption='[[6j21]], [[Resolution|resolution]] 3.20&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[6j21]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6J21 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6J21 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[6j21]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_virus_T4 Escherichia virus T4] and [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6J21 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6J21 FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GBQ:5-[[(2~{R},3~{S})-2-[(1~{R})-1-[3,5-bis(trifluoromethyl)phenyl]ethoxy]-3-(4-fluorophenyl)morpholin-4-yl]methyl]-1,2-dihydro-1,2,4-triazol-3-one'>GBQ</scene>, <scene name='pdbligand=OLC:(2R)-2,3-DIHYDROXYPROPYL+(9Z)-OCTADEC-9-ENOATE'>OLC</scene></td></tr>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.2&#8491;</td></tr>
-<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Lysozyme Lysozyme], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.2.1.17 3.2.1.17] </span></td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GBQ:5-[[(2~{R},3~{S})-2-[(1~{R})-1-[3,5-bis(trifluoromethyl)phenyl]ethoxy]-3-(4-fluorophenyl)morpholin-4-yl]methyl]-1,2-dihydro-1,2,4-triazol-3-one'>GBQ</scene>, <scene name='pdbligand=OLC:(2R)-2,3-DIHYDROXYPROPYL+(9Z)-OCTADEC-9-ENOATE'>OLC</scene></td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6j21 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6j21 OCA], [http://pdbe.org/6j21 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6j21 RCSB], [http://www.ebi.ac.uk/pdbsum/6j21 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6j21 ProSAT]</span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6j21 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6j21 OCA], [https://pdbe.org/6j21 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6j21 RCSB], [https://www.ebi.ac.uk/pdbsum/6j21 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6j21 ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[http://www.uniprot.org/uniprot/NK1R_HUMAN NK1R_HUMAN]] This is a receptor for the tachykinin neuropeptide substance P. It is probably associated with G proteins that activate a phosphatidylinositol-calcium second messenger system. The rank order of affinity of this receptor to tachykinins is: substance P > substance K > neuromedin-K.
+[https://www.uniprot.org/uniprot/NK1R_HUMAN NK1R_HUMAN] This is a receptor for the tachykinin neuropeptide substance P. It is probably associated with G proteins that activate a phosphatidylinositol-calcium second messenger system. The rank order of affinity of this receptor to tachykinins is: substance P > substance K > neuromedin-K.[https://www.uniprot.org/uniprot/ENLYS_BPT4 ENLYS_BPT4] Endolysin with lysozyme activity that degrades host peptidoglycans and participates with the holin and spanin proteins in the sequential events which lead to the programmed host cell lysis releasing the mature viral particles. Once the holin has permeabilized the host cell membrane, the endolysin can reach the periplasm and break down the peptidoglycan layer.<ref>PMID:22389108</ref>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 23: / Line 23: @@
 __TOC__
 </StructureSection>
-[[Category: Lysozyme]]
+[[Category: Escherichia virus T4]]
-[[Category: Chen, S]]
+[[Category: Homo sapiens]]
-[[Category: Lu, M]]
+[[Category: Large Structures]]
-[[Category: Wu, B]]
+[[Category: Chen S]]
-[[Category: Zhang, H]]
+[[Category: Lu M]]
-[[Category: Zhao, Q]]
+[[Category: Wu B]]
-[[Category: Antagonist]]
+[[Category: Zhang H]]
-[[Category: Complex]]
+[[Category: Zhao Q]]
-[[Category: Gpcr]]
-[[Category: Membrane protein]]
-[[Category: Signalling protein]]

6j21

From Proteopedia

Revision as of 09:58, 22 November 2023

Crystal structure of the human NK1 substance P receptor

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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