8uvb

From Proteopedia

(Difference between revisions)

Current revision

Structure of NaCT-PF4a complex

Structural highlights

8uvb is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	Electron Microscopy, Resolution 2.13Å
Ligands:	,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

S13A5_HUMAN Undetermined early-onset epileptic encephalopathy;Amelocerebrohypohidrotic syndrome;Pyridoxine-dependent epilepsy. The disease is caused by variants affecting the gene represented in this entry.

Function

S13A5_HUMAN High-affinity sodium/citrate cotransporter that mediates citrate entry into cells. The transport process is electrogenic; it is the trivalent form of citrate rather than the divalent form that is recognized as a substrate. May facilitate the utilization of circulating citrate for the generation of metabolic energy and for the synthesis of fatty acids and cholesterol.^[1] ^[2]

Publication Abstract from PubMed

The human high-affinity sodium-dicarboxylate cotransporter (NaDC3) imports various substrates into the cell as tricarboxylate acid cycle intermediates, lipid biosynthesis precursors and signaling molecules. Understanding the cellular signaling process and developing inhibitors require knowledge of the structural basis of the dicarboxylate specificity and inhibition mechanism of NaDC3. To this end, we determined the cryo-electron microscopy structures of NaDC3 in various dimers, revealing the protomer in three conformations: outward-open C(o), outward-occluded C(oo) and inward-open C(i). A dicarboxylate is first bound and recognized in C(o) and how the substrate interacts with NaDC3 in C(oo) likely helps to further determine the substrate specificity. A phenylalanine from the scaffold domain interacts with the bound dicarboxylate in the C(oo) state and modulates the kinetic barrier to the transport domain movement. Structural comparison of an inhibitor-bound structure of NaDC3 to that of the sodium-dependent citrate transporter suggests ways for making an inhibitor that is specific for NaDC3.

Substrate translocation and inhibition in human dicarboxylate transporter NaDC3.,Li Y, Song J, Mikusevic V, Marden JJ, Becerril A, Kuang H, Wang B, Rice WJ, Mindell JA, Wang DN Nat Struct Mol Biol. 2024 Dec 2. doi: 10.1038/s41594-024-01433-0. PMID:39622972^[3]

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

References

↑ Inoue K, Zhuang L, Ganapathy V. Human Na+ -coupled citrate transporter: primary structure, genomic organization, and transport function. Biochem Biophys Res Commun. 2002 Dec 6;299(3):465-71. doi:, 10.1016/s0006-291x(02)02669-4. PMID:12445824 doi:http://dx.doi.org/10.1016/s0006-291x(02)02669-4
↑ Hardies K, de Kovel CG, Weckhuysen S, Asselbergh B, Geuens T, Deconinck T, Azmi A, May P, Brilstra E, Becker F, Barisic N, Craiu D, Braun KP, Lal D, Thiele H, Schubert J, Weber Y, van 't Slot R, Nurnberg P, Balling R, Timmerman V, Lerche H, Maudsley S, Helbig I, Suls A, Koeleman BP, De Jonghe P. Recessive mutations in SLC13A5 result in a loss of citrate transport and cause neonatal epilepsy, developmental delay and teeth hypoplasia. Brain. 2015 Nov;138(Pt 11):3238-50. doi: 10.1093/brain/awv263. Epub 2015 Sep 17. PMID:26384929 doi:http://dx.doi.org/10.1093/brain/awv263
↑ Li Y, Song J, Mikusevic V, Marden JJ, Becerril A, Kuang H, Wang B, Rice WJ, Mindell JA, Wang DN. Substrate translocation and inhibition in human dicarboxylate transporter NaDC3. Nat Struct Mol Biol. 2024 Dec 2. PMID:39622972 doi:10.1038/s41594-024-01433-0

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/8uvb"

@@ Line 5: / Line 5: @@
 <table><tr><td colspan='2'>[[8uvb]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8UVB OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8UVB FirstGlance]. <br>
 </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 2.13&#8491;</td></tr>
-<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=XKC:(2~{R})-2-[2-(2-methoxy-5-methyl-pyridin-3-yl)ethyl]-2-oxidanyl-butanedioic+acid'>XKC</scene></td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=XKC:(2R)-2-hydroxy-2-[2-(2-methoxy-5-methylpyridin-3-yl)ethyl]butanedioic+acid'>XKC</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=8uvb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8uvb OCA], [https://pdbe.org/8uvb PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8uvb RCSB], [https://www.ebi.ac.uk/pdbsum/8uvb PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8uvb ProSAT]</span></td></tr>
 </table>

8uvb

From Proteopedia

Current revision

Structure of NaCT-PF4a complex

Structural highlights

Disease

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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