7zly

From Proteopedia

(Difference between revisions)

Current revision

Crystal structure of human GPCR Niacin receptor (HCA2) expressed from Spodoptera frugiperda

Structural highlights

7zly is a 1 chain structure with sequence from Escherichia coli 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 2.7Å
Ligands:	,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

C562_ECOLX Electron-transport protein of unknown function.HCAR2_HUMAN Acts as a high affinity receptor for both nicotinic acid (also known as niacin) and (D)-beta-hydroxybutyrate and mediates increased adiponectin secretion and decreased lipolysis through G(i)-protein-mediated inhibition of adenylyl cyclase. This pharmacological effect requires nicotinic acid doses that are much higher than those provided by a normal diet. Mediates nicotinic acid-induced apoptosis in mature neutrophils. Receptor activation by nicotinic acid results in reduced cAMP levels which may affect activity of cAMP-dependent protein kinase A and phosphorylation of target proteins, leading to neutrophil apoptosis. The rank order of potency for the displacement of nicotinic acid binding is 5-methyl pyrazole-3-carboxylic acid = pyridine-3-acetic acid > acifran > 5-methyl nicotinic acid = acipimox >> nicotinuric acid = nicotinamide.^[1]

Publication Abstract from PubMed

The hydroxycarboxylic acid receptor 2 (HCA2) agonist niacin has been used as treatment for dyslipidemia for several decades albeit with skin flushing as a common side-effect in treated individuals. Extensive efforts have been made to identify HCA2 targeting lipid lowering agents with fewer adverse effects, despite little being known about the molecular basis of HCA2 mediated signalling. Here, we report the cryo-electron microscopy structure of the HCA2-G(i) signalling complex with the potent agonist MK-6892, along with crystal structures of HCA2 in inactive state. These structures, together with comprehensive pharmacological analysis, reveal the ligand binding mode and activation and signalling mechanisms of HCA2. This study elucidates the structural determinants essential for HCA2 mediated signalling and provides insights into ligand discovery for HCA2 and related receptors.

Structural insights into the human niacin receptor HCA2-G(i) signalling complex.,Yang Y, Kang HJ, Gao R, Wang J, Han GW, DiBerto JF, Wu L, Tong J, Qu L, Wu Y, Pileski R, Li X, Zhang XC, Zhao S, Kenakin T, Wang Q, Stevens RC, Peng W, Roth BL, Rao Z, Liu ZJ Nat Commun. 2023 Mar 27;14(1):1692. doi: 10.1038/s41467-023-37177-6. PMID:36973264^[2]

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

References

↑ Kostylina G, Simon D, Fey MF, Yousefi S, Simon HU. Neutrophil apoptosis mediated by nicotinic acid receptors (GPR109A). Cell Death Differ. 2008 Jan;15(1):134-42. PMID:17932499 doi:10.1038/sj.cdd.4402238
↑ Yang Y, Kang HJ, Gao R, Wang J, Han GW, DiBerto JF, Wu L, Tong J, Qu L, Wu Y, Pileski R, Li X, Zhang XC, Zhao S, Kenakin T, Wang Q, Stevens RC, Peng W, Roth BL, Rao Z, Liu ZJ. Structural insights into the human niacin receptor HCA2-G(i) signalling complex. Nat Commun. 2023 Mar 27;14(1):1692. PMID:36973264 doi:10.1038/s41467-023-37177-6

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/7zly"

@@ Line 4: / Line 4: @@
 == Structural highlights ==
 <table><tr><td colspan='2'>[[7zly]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli] 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=7ZLY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7ZLY FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=OLA:OLEIC+ACID'>OLA</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]] 2.7&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=OLA:OLEIC+ACID'>OLA</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'>[https://proteopedia.org/fgij/fg.htm?mol=7zly FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7zly OCA], [https://pdbe.org/7zly PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7zly RCSB], [https://www.ebi.ac.uk/pdbsum/7zly PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7zly ProSAT]</span></td></tr>
 </table>

7zly

From Proteopedia

Current revision

Crystal structure of human GPCR Niacin receptor (HCA2) expressed from Spodoptera frugiperda

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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