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5o28

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E. coli FolD apo

Structural highlights

5o28 is a 4 chain structure with sequence from Escherichia coli K-12. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 1.89Å
Ligands:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

FOLD_ECOLI Catalyzes the oxidation of 5,10-methylenetetrahydrofolate to 5,10-methenyltetrahydrofolate and then the hydrolysis of 5,10-methenyltetrahydrofolate to 10-formyltetrahydrofolate. This enzyme is specific for NADP.^[1]

Publication Abstract from PubMed

The natural product carolacton is a macrolide keto-carboxylic acid produced by the myxobacterium Sorangium cellulosum, and was originally described as an antibacterial compound. Here we show that carolacton targets FolD, a key enzyme from the folate-dependent C1 metabolism. We characterize the interaction between bacterial FolD and carolacton biophysically, structurally and biochemically. Carolacton binds FolD with nanomolar affinity, and the crystal structure of the FolD-carolacton complex reveals the mode of binding. We show that the human FolD orthologs, MTHFD1 and MTHFD2, are also inhibited in the low nM range, and that micromolar concentrations of carolacton inhibit the growth of cancer cell lines. As mitochondrial MTHFD2 is known to be upregulated in cancer cells, it may be possible to use carolacton as an inhibitor tool compound to assess MTHFD2 as an anti-cancer target.

The natural product carolacton inhibits folate-dependent C1 metabolism by targeting FolD/MTHFD.,Fu C, Sikandar A, Donner J, Zaburannyi N, Herrmann J, Reck M, Wagner-Dobler I, Koehnke J, Muller R Nat Commun. 2017 Nov 16;8(1):1529. doi: 10.1038/s41467-017-01671-5. PMID:29142318^[2]

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

References

↑ D'Ari L, Rabinowitz JC. Purification, characterization, cloning, and amino acid sequence of the bifunctional enzyme 5,10-methylenetetrahydrofolate dehydrogenase/5,10-methenyltetrahydrofolate cyclohydrolase from Escherichia coli. J Biol Chem. 1991 Dec 15;266(35):23953-8. PMID:1748668
↑ Fu C, Sikandar A, Donner J, Zaburannyi N, Herrmann J, Reck M, Wagner-Dobler I, Koehnke J, Muller R. The natural product carolacton inhibits folate-dependent C1 metabolism by targeting FolD/MTHFD. Nat Commun. 2017 Nov 16;8(1):1529. doi: 10.1038/s41467-017-01671-5. PMID:29142318 doi:http://dx.doi.org/10.1038/s41467-017-01671-5

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/5o28"

Categories: Escherichia coli K-12 | Large Structures | Koehnke J | Sikandar A

@@ Line 1: / Line 1: @@
 ==E. coli FolD apo==
-<StructureSection load='5o28' size='340' side='right' caption='[[5o28]], [[Resolution|resolution]] 1.89&Aring;' scene=''>
+<StructureSection load='5o28' size='340' side='right'caption='[[5o28]], [[Resolution|resolution]] 1.89&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5o28]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5O28 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5O28 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[5o28]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli_K-12 Escherichia coli K-12]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5O28 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5O28 FirstGlance]. <br>
-</td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=MLY:N-DIMETHYL-LYSINE'>MLY</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]] 1.89&#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=5o28 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5o28 OCA], [http://pdbe.org/5o28 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5o28 RCSB], [http://www.ebi.ac.uk/pdbsum/5o28 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5o28 ProSAT]</span></td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MLY:N-DIMETHYL-LYSINE'>MLY</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=5o28 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5o28 OCA], [https://pdbe.org/5o28 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5o28 RCSB], [https://www.ebi.ac.uk/pdbsum/5o28 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5o28 ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[http://www.uniprot.org/uniprot/FOLD_ECOLI FOLD_ECOLI]] Catalyzes the oxidation of 5,10-methylenetetrahydrofolate to 5,10-methenyltetrahydrofolate and then the hydrolysis of 5,10-methenyltetrahydrofolate to 10-formyltetrahydrofolate. This enzyme is specific for NADP.<ref>PMID:1748668</ref>
+[https://www.uniprot.org/uniprot/FOLD_ECOLI FOLD_ECOLI] Catalyzes the oxidation of 5,10-methylenetetrahydrofolate to 5,10-methenyltetrahydrofolate and then the hydrolysis of 5,10-methenyltetrahydrofolate to 10-formyltetrahydrofolate. This enzyme is specific for NADP.<ref>PMID:1748668</ref>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 22: / Line 23: @@
 __TOC__
 </StructureSection>
-[[Category: Koehnke, J]]
+[[Category: Escherichia coli K-12]]
-[[Category: Sikandar, A]]
+[[Category: Large Structures]]
-[[Category: Carolacton]]
+[[Category: Koehnke J]]
-[[Category: Fold]]
+[[Category: Sikandar A]]
-[[Category: Inhibitor]]
-[[Category: Natural product]]
-[[Category: Oxidoreductase]]

5o28

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Current revision

E. coli FolD apo

Structural highlights

Function

Publication Abstract from PubMed

References

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