5w6o

From Proteopedia

(Difference between revisions)

Current revision

Choline Kinase Alpha in Complex with TCD-717

Structural highlights

5w6o 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:	X-ray diffraction, Resolution 2.35Å
Ligands:	, ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

CHKA_HUMAN Has a key role in phospholipid biosynthesis and may contribute to tumor cell growth. Catalyzes the first step in phosphatidylcholine biosynthesis. Contributes to phosphatidylethanolamine biosynthesis. Phosphorylates choline and ethanolamine. Has higher activity with choline.^[1]

Publication Abstract from PubMed

Choline kinase alpha (ChoKalpha) is an enzyme that is upregulated in many types of cancer and has been shown to be tumorigenic. As such, it makes a promising target for inhibiting tumor growth. Though there have been several inhibitors synthesized for ChoKalpha, not all of them demonstrate the same efficacy in vivo, though the reasons behind this difference in potency are not clear. One particular inhibitor, designated TCD-717, has recently completed phase I clinical trials. Cell culture and in vitro studies support the powerful inhibitory effect TCD-717 has on ChoKalpha, but an examination of the inhibitor's interaction with the ChoKalpha enzyme has been missing prior to this work. Here we detail the 2.35 A structure of ChoKalpha in complex with TCD-717. Examination of this structure in conjunction with kinetic assays reveals that TCD-717 does not bind directly in the choline pocket as do previously characterized ChoKalpha inhibitors, but rather in a proximal but novel location near the surface of the enzyme. The unique binding site identified for TCD-717 lends insight for the future design of more potent in vivo inhibitors for ChoKalpha.

Identification of a Unique Inhibitor-Binding Site on Choline Kinase alpha.,Kall SL, Delikatny EJ, Lavie A Biochemistry. 2018 Feb 8. doi: 10.1021/acs.biochem.7b01257. PMID:29389115^[2]

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

References

↑ Gallego-Ortega D, Ramirez de Molina A, Ramos MA, Valdes-Mora F, Barderas MG, Sarmentero-Estrada J, Lacal JC. Differential role of human choline kinase alpha and beta enzymes in lipid metabolism: implications in cancer onset and treatment. PLoS One. 2009 Nov 12;4(11):e7819. doi: 10.1371/journal.pone.0007819. PMID:19915674 doi:10.1371/journal.pone.0007819
↑ Kall SL, Delikatny EJ, Lavie A. Identification of a Unique Inhibitor-Binding Site on Choline Kinase alpha. Biochemistry. 2018 Feb 8. doi: 10.1021/acs.biochem.7b01257. PMID:29389115 doi:http://dx.doi.org/10.1021/acs.biochem.7b01257

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/5w6o"

Categories: Homo sapiens | Large Structures | Kall SK | Lavie A

@@ Line 1: / Line 1: @@
 ==Choline Kinase Alpha in Complex with TCD-717==
-<StructureSection load='5w6o' size='340' side='right' caption='[[5w6o]], [[Resolution|resolution]] 2.35&Aring;' scene=''>
+<StructureSection load='5w6o' size='340' side='right'caption='[[5w6o]], [[Resolution|resolution]] 2.35&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5w6o]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5W6O OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5W6O FirstGlance]. <br>
+<table><tr><td colspan='2'>[[5w6o]] 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=5W6O OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5W6O FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=9X1:1,1-[[1,1-biphenyl]-4,4-diylbis(methylene)]bis{4-[(4-chlorophenyl)(methyl)amino]quinolin-1-ium}'>9X1</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=MES:2-(N-MORPHOLINO)-ETHANESULFONIC+ACID'>MES</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]] 2.35&#8491;</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=5w6o FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5w6o OCA], [http://pdbe.org/5w6o PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5w6o RCSB], [http://www.ebi.ac.uk/pdbsum/5w6o PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5w6o ProSAT]</span></td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=9X1:1,1-[[1,1-biphenyl]-4,4-diylbis(methylene)]bis{4-[(4-chlorophenyl)(methyl)amino]quinolin-1-ium}'>9X1</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=MES:2-(N-MORPHOLINO)-ETHANESULFONIC+ACID'>MES</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=5w6o FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5w6o OCA], [https://pdbe.org/5w6o PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5w6o RCSB], [https://www.ebi.ac.uk/pdbsum/5w6o PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5w6o ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[http://www.uniprot.org/uniprot/CHKA_HUMAN CHKA_HUMAN]] Has a key role in phospholipid biosynthesis and may contribute to tumor cell growth. Catalyzes the first step in phosphatidylcholine biosynthesis. Contributes to phosphatidylethanolamine biosynthesis. Phosphorylates choline and ethanolamine. Has higher activity with choline.<ref>PMID:19915674</ref>
+[https://www.uniprot.org/uniprot/CHKA_HUMAN CHKA_HUMAN] Has a key role in phospholipid biosynthesis and may contribute to tumor cell growth. Catalyzes the first step in phosphatidylcholine biosynthesis. Contributes to phosphatidylethanolamine biosynthesis. Phosphorylates choline and ethanolamine. Has higher activity with choline.<ref>PMID:19915674</ref>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 18: / Line 19: @@
 </div>
 <div class="pdbe-citations 5w6o" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Choline kinase 3D structures|Choline kinase 3D structures]]
 == References ==
 <references/>
 __TOC__
 </StructureSection>
-[[Category: Kall, S K]]
+[[Category: Homo sapiens]]
-[[Category: Lavie, A]]
+[[Category: Large Structures]]
-[[Category: Drug]]
+[[Category: Kall SK]]
-[[Category: Enzyme]]
+[[Category: Lavie A]]
-[[Category: Inhibitor]]
-[[Category: Transferase-inhibitor complex]]

5w6o

From Proteopedia

Current revision

Choline Kinase Alpha in Complex with TCD-717

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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