6fcx

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
Current revision (09:01, 9 April 2025) (edit) (undo)
 
(2 intermediate revisions not shown.)
Line 1: Line 1:
-
'''Unreleased structure'''
 
-
The entry 6fcx is ON HOLD
+
==Structure of human 5,10-methylenetetrahydrofolate reductase (MTHFR)==
 +
<StructureSection load='6fcx' size='340' side='right'caption='[[6fcx]], [[Resolution|resolution]] 2.50&Aring;' scene=''>
 +
== Structural highlights ==
 +
<table><tr><td colspan='2'>[[6fcx]] 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=6FCX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6FCX FirstGlance]. <br>
 +
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.5&#8491;</td></tr>
 +
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CIT:CITRIC+ACID'>CIT</scene>, <scene name='pdbligand=FAD:FLAVIN-ADENINE+DINUCLEOTIDE'>FAD</scene>, <scene name='pdbligand=SAH:S-ADENOSYL-L-HOMOCYSTEINE'>SAH</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=6fcx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6fcx OCA], [https://pdbe.org/6fcx PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6fcx RCSB], [https://www.ebi.ac.uk/pdbsum/6fcx PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6fcx ProSAT]</span></td></tr>
 +
</table>
 +
== Disease ==
 +
[https://www.uniprot.org/uniprot/MTHR_HUMAN MTHR_HUMAN] Thoracolumbosacral spina bifida cystica;Cervicothoracic spina bifida cystica;Lumbosacral spina bifida cystica;Homocystinuria due to methylene tetrahydrofolate reductase deficiency;Cervicothoracic spina bifida aperta;Upper thoracic spina bifida aperta;Lumbosacral spina bifida aperta;Thoracolumbosacral spina bifida aperta;Methotrexate toxicity or dose selection;Cervical spina bifida cystica;Non rare thrombophilia;Upper thoracic spina bifida cystica;Total spina bifida aperta;Total spina bifida cystica;Isolated anencephaly/exencephaly;Cervical spina bifida aperta. The disease is caused by mutations affecting the gene represented in this entry. Disease susceptibility is associated with variations affecting the gene represented in this entry. Disease susceptibility is associated with variations affecting the gene represented in this entry. Disease susceptibility is associated with variations affecting the gene represented in this entry.
 +
== Function ==
 +
[https://www.uniprot.org/uniprot/MTHR_HUMAN MTHR_HUMAN] Catalyzes the conversion of 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate, a co-substrate for homocysteine remethylation to methionine.<ref>PMID:25736335</ref>
 +
<div style="background-color:#fffaf0;">
 +
== Publication Abstract from PubMed ==
 +
The folate and methionine cycles are crucial for biosynthesis of lipids, nucleotides and proteins, and production of the methyl donor S-adenosylmethionine (SAM). 5,10-methylenetetrahydrofolate reductase (MTHFR) represents a key regulatory connection between these cycles, generating 5-methyltetrahydrofolate for initiation of the methionine cycle, and undergoing allosteric inhibition by its end product SAM. Our 2.5 A resolution crystal structure of human MTHFR reveals a unique architecture, appending the well-conserved catalytic TIM-barrel to a eukaryote-only SAM-binding domain. The latter domain of novel fold provides the predominant interface for MTHFR homo-dimerization, positioning the N-terminal serine-rich phosphorylation region near the C-terminal SAM-binding domain. This explains how MTHFR phosphorylation, identified on 11 N-terminal residues (16 in total), increases sensitivity to SAM binding and inhibition. Finally, we demonstrate that the 25-amino-acid inter-domain linker enables conformational plasticity and propose it to be a key mediator of SAM regulation. Together, these results provide insight into the molecular regulation of MTHFR.
-
Authors: Bezerra, G.A., Kopec, J., Rembeza, E., Oberholzer, A.E., Sorrel, F., Ellis, K., Kupinska, K., Krojer, T., Burgess-Brown, N., von Delft, F., Arrowsmith, C., Edwards, E., Bountra, C., Froese, S.D., Baumgartner, M., Yue, W.W., Structural Genomics Consortium (SGC)
+
Structural basis for the regulation of human 5,10-methylenetetrahydrofolate reductase by phosphorylation and S-adenosylmethionine inhibition.,Froese DS, Kopec J, Rembeza E, Bezerra GA, Oberholzer AE, Suormala T, Lutz S, Chalk R, Borkowska O, Baumgartner MR, Yue WW Nat Commun. 2018 Jun 11;9(1):2261. doi: 10.1038/s41467-018-04735-2. PMID:29891918<ref>PMID:29891918</ref>
-
Description: Structure of a human folate metabolizing enzyme
+
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-
[[Category: Unreleased Structures]]
+
</div>
-
[[Category: Burgess-Brown, N]]
+
<div class="pdbe-citations 6fcx" style="background-color:#fffaf0;"></div>
-
[[Category: Oberholzer, A.E]]
+
 
-
[[Category: Bezerra, G.A]]
+
==See Also==
-
[[Category: Yue, W.W]]
+
*[[Methylenetetrahydrofolate reductase 3D structures|Methylenetetrahydrofolate reductase 3D structures]]
-
[[Category: Baumgartner, M]]
+
== References ==
-
[[Category: Kopec, J]]
+
<references/>
-
[[Category: Von Delft, F]]
+
__TOC__
-
[[Category: Edwards, E]]
+
</StructureSection>
-
[[Category: Arrowsmith, C]]
+
[[Category: Homo sapiens]]
-
[[Category: Sorrel, F]]
+
[[Category: Large Structures]]
-
[[Category: Ellis, K]]
+
[[Category: Arrowsmith C]]
-
[[Category: Structural Genomics Consortium (Sgc)]]
+
[[Category: Baumgartner M]]
-
[[Category: Krojer, T]]
+
[[Category: Bezerra GA]]
-
[[Category: Froese, S.D]]
+
[[Category: Borkowska O]]
-
[[Category: Rembeza, E]]
+
[[Category: Bountra C]]
-
[[Category: Bountra, C]]
+
[[Category: Burgess-Brown N]]
-
[[Category: Kupinska, K]]
+
[[Category: Chalk R]]
 +
[[Category: Edwards A]]
 +
[[Category: Ellis K]]
 +
[[Category: Froese DS]]
 +
[[Category: Kopec J]]
 +
[[Category: Krojer T]]
 +
[[Category: Kupinska K]]
 +
[[Category: Oberholzer AE]]
 +
[[Category: Rembeza E]]
 +
[[Category: Sorrell FJ]]
 +
[[Category: Von Delft F]]
 +
[[Category: Yue WW]]

Current revision

Structure of human 5,10-methylenetetrahydrofolate reductase (MTHFR)

PDB ID 6fcx

Drag the structure with the mouse to rotate

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/6fcx"
Personal tools