1a4i: Difference between revisions

From Proteopedia
Jump to navigation Jump to search
← Older edit
No edit summary
No edit summary
 
(6 intermediate revisions by the same user not shown)
Line 1: Line 1:
==HUMAN TETRAHYDROFOLATE DEHYDROGENASE / CYCLOHYDROLASE==
==HUMAN TETRAHYDROFOLATE DEHYDROGENASE / CYCLOHYDROLASE==
<StructureSection load='1a4i' size='340' side='right' caption='[[1a4i]], [[Resolution|resolution]] 1.50&Aring;' scene=''>
<StructureSection load='1a4i' size='340' side='right'caption='[[1a4i]], [[Resolution|resolution]] 1.50&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[1a4i]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1A4I OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1A4I FirstGlance]. <br>
<table><tr><td colspan='2'>[[1a4i]] 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=1A4I OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1A4I FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=NDP:NADPH+DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NDP</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]] 1.5&#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=1a4i FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1a4i OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1a4i RCSB], [http://www.ebi.ac.uk/pdbsum/1a4i PDBsum]</span></td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NDP:NADPH+DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NDP</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=1a4i FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1a4i OCA], [https://pdbe.org/1a4i PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1a4i RCSB], [https://www.ebi.ac.uk/pdbsum/1a4i PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1a4i ProSAT]</span></td></tr>
</table>
</table>
== Disease ==
== Disease ==
[[http://www.uniprot.org/uniprot/C1TC_HUMAN C1TC_HUMAN]] Defects in MTHFD1 may be a cause of susceptibility to folate-sensitive neural tube defects (FS-NTD) [MIM:[http://omim.org/entry/601634 601634]]. The most common NTDs are open spina bifida (myelomeningocele) and anencephaly. Genetic defects in MTHFD1 may affect the risk of spina bifida via the maternal rather than the embryonic genotype.<ref>PMID:9611072</ref> <ref>PMID:12384833</ref> <ref>PMID:16552426</ref>  Genetic variation in MTHFD1 could be associated with susceptibility to colorectal cancer (CRC) [MIM:[http://omim.org/entry/114500 114500]].  
[https://www.uniprot.org/uniprot/C1TC_HUMAN C1TC_HUMAN] Defects in MTHFD1 may be a cause of susceptibility to folate-sensitive neural tube defects (FS-NTD) [MIM:[https://omim.org/entry/601634 601634]. The most common NTDs are open spina bifida (myelomeningocele) and anencephaly. Genetic defects in MTHFD1 may affect the risk of spina bifida via the maternal rather than the embryonic genotype.<ref>PMID:9611072</ref> <ref>PMID:12384833</ref> <ref>PMID:16552426</ref>  Genetic variation in MTHFD1 could be associated with susceptibility to colorectal cancer (CRC) [MIM:[https://omim.org/entry/114500 114500].
== Function ==
== Function ==
 
[https://www.uniprot.org/uniprot/C1TC_HUMAN C1TC_HUMAN]
== Evolutionary Conservation ==
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
Check<jmol>
   <jmolCheckbox>
   <jmolCheckbox>
     <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/a4/1a4i_consurf.spt"</scriptWhenChecked>
     <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/a4/1a4i_consurf.spt"</scriptWhenChecked>
     <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
     <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
     <text>to colour the structure by Evolutionary Conservation</text>
     <text>to colour the structure by Evolutionary Conservation</text>
   </jmolCheckbox>
   </jmolCheckbox>
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/chain_selection.php?pdb_ID=2ata ConSurf].
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1a4i ConSurf].
<div style="clear:both"></div>
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
BACKGROUND: The interconversion of two major folate one-carbon donors occurs through the sequential activities of NAD(P)-dependent methylene[H4]folate dehydrogenase (D) and methenyl[H4]folate cyclohydrolase (C). These activities often coexist as part of a multifunctional enzyme and there are several lines of evidence suggesting that their substrates bind at overlapping sites. Little is known, however, about the nature of this site or the identity of the active-site residues for this enzyme family. RESULTS: We have determined, to 1.5 A resolution, the structure of a dimer of the D/C domain of the human trifunctional cytosolic enzyme with bound NADP cofactor, using the MAD technique. The D/C subunit is composed of two alpha/beta domains that assemble to form a wide cleft. The cleft walls are lined with highly conserved residues and NADP is bound along one wall. The NADP-binding domain has a Rossmann fold, characterized by a modified diphosphate-binding loop fingerprint-GXSXXXG. Dimerization occurs by antiparallel interaction of two NADP-binding domains. Superposition of the two subunits indicates domain motion occurs about a well-defined hinge region. CONCLUSIONS: Analysis of the structure suggests strongly that folate-binding sites for both activities are within the cleft, providing direct support for the proposed overlapping site model. The orientation of the nicotinamide ring suggests that in the dehydrogenase-catalyzed reaction hydride transfer occurs to the pro-R side of the ring. The identity of the cyclohydrolase active site is not obvious. We propose that a conserved motif-Tyr52-X-X-X-Lys56- and/or a Ser49-Gln100-Pro102 triplet have a role in this activity.
The 3-D structure of a folate-dependent dehydrogenase/cyclohydrolase bifunctional enzyme at 1.5 A resolution.,Allaire M, Li Y, MacKenzie RE, Cygler M Structure. 1998 Feb 15;6(2):173-82. PMID:9519408<ref>PMID:9519408</ref>


From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
==See Also==
</div>
*[[Cyclohydrolase 3D structures|Cyclohydrolase 3D structures]]
== References ==
== References ==
<references/>
<references/>
Line 33: Line 30:
</StructureSection>
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Allaire, M]]
[[Category: Large Structures]]
[[Category: Cygler, M]]
[[Category: Allaire M]]
[[Category: Li, Y]]
[[Category: Cygler M]]
[[Category: Mackenzie, R E]]
[[Category: Li Y]]
[[Category: Bifunctional]]
[[Category: Mackenzie RE]]
[[Category: Cyclohydrolase]]
[[Category: Dehydrogenase]]
[[Category: Folate]]
[[Category: Oxidoreductase]]
[[Category: Thf]]

Latest revision as of 09:27, 7 February 2024

HUMAN TETRAHYDROFOLATE DEHYDROGENASE / CYCLOHYDROLASEHUMAN TETRAHYDROFOLATE DEHYDROGENASE / CYCLOHYDROLASE

Structural highlights

1a4i 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 1.5Å
Ligands:
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

C1TC_HUMAN Defects in MTHFD1 may be a cause of susceptibility to folate-sensitive neural tube defects (FS-NTD) [MIM:601634. The most common NTDs are open spina bifida (myelomeningocele) and anencephaly. Genetic defects in MTHFD1 may affect the risk of spina bifida via the maternal rather than the embryonic genotype.[1] [2] [3] Genetic variation in MTHFD1 could be associated with susceptibility to colorectal cancer (CRC) [MIM:114500.

Function

C1TC_HUMAN

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

See Also

References

  1. ↑ Hol FA, van der Put NM, Geurds MP, Heil SG, Trijbels FJ, Hamel BC, Mariman EC, Blom HJ. Molecular genetic analysis of the gene encoding the trifunctional enzyme MTHFD (methylenetetrahydrofolate-dehydrogenase, methenyltetrahydrofolate-cyclohydrolase, formyltetrahydrofolate synthetase) in patients with neural tube defects. Clin Genet. 1998 Feb;53(2):119-25. PMID:9611072
  2. ↑ Brody LC, Conley M, Cox C, Kirke PN, McKeever MP, Mills JL, Molloy AM, O'Leary VB, Parle-McDermott A, Scott JM, Swanson DA. A polymorphism, R653Q, in the trifunctional enzyme methylenetetrahydrofolate dehydrogenase/methenyltetrahydrofolate cyclohydrolase/formyltetrahydrofolate synthetase is a maternal genetic risk factor for neural tube defects: report of the Birth Defects Research Group. Am J Hum Genet. 2002 Nov;71(5):1207-15. Epub 2002 Oct 16. PMID:12384833 doi:S0002-9297(07)60415-7
  3. ↑ Parle-McDermott A, Kirke PN, Mills JL, Molloy AM, Cox C, O'Leary VB, Pangilinan F, Conley M, Cleary L, Brody LC, Scott JM. Confirmation of the R653Q polymorphism of the trifunctional C1-synthase enzyme as a maternal risk for neural tube defects in the Irish population. Eur J Hum Genet. 2006 Jun;14(6):768-72. PMID:16552426 doi:5201603

1a4i, resolution 1.50Å

Drag the structure with the mouse to rotate

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA
Retrieved from "https://proteopedia.openfox.io/wiki/index.php?title=1a4i&oldid=4039890"