2w3a: Difference between revisions

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== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[2w3a]] 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=2W3A OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2W3A FirstGlance]. <br>
<table><tr><td colspan='2'>[[2w3a]] 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=2W3A OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2W3A FirstGlance]. <br>
</td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NDP:NADPH+DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NDP</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=TOP:TRIMETHOPRIM'>TOP</scene><br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NDP:NADPH+DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NDP</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=TOP:TRIMETHOPRIM'>TOP</scene></td></tr>
<tr><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2c2s|2c2s]], [[2w3m|2w3m]], [[1dhf|1dhf]], [[2dhf|2dhf]], [[1s3w|1s3w]], [[2w3b|2w3b]], [[1s3v|1s3v]], [[1pd8|1pd8]], [[1dls|1dls]], [[1dlr|1dlr]], [[1u72|1u72]], [[1ohk|1ohk]], [[1yho|1yho]], [[2c2t|2c2t]], [[1ohj|1ohj]], [[1pd9|1pd9]], [[1kmv|1kmv]], [[1hfr|1hfr]], [[1mvt|1mvt]], [[1u71|1u71]], [[1kms|1kms]], [[1pdb|1pdb]], [[1hfq|1hfq]], [[1s3u|1s3u]], [[1drf|1drf]], [[1mvs|1mvs]], [[1hfp|1hfp]], [[1boz|1boz]]</td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2c2s|2c2s]], [[2w3m|2w3m]], [[1dhf|1dhf]], [[2dhf|2dhf]], [[1s3w|1s3w]], [[2w3b|2w3b]], [[1s3v|1s3v]], [[1pd8|1pd8]], [[1dls|1dls]], [[1dlr|1dlr]], [[1u72|1u72]], [[1ohk|1ohk]], [[1yho|1yho]], [[2c2t|2c2t]], [[1ohj|1ohj]], [[1pd9|1pd9]], [[1kmv|1kmv]], [[1hfr|1hfr]], [[1mvt|1mvt]], [[1u71|1u71]], [[1kms|1kms]], [[1pdb|1pdb]], [[1hfq|1hfq]], [[1s3u|1s3u]], [[1drf|1drf]], [[1mvs|1mvs]], [[1hfp|1hfp]], [[1boz|1boz]]</td></tr>
<tr><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Dihydrofolate_reductase Dihydrofolate reductase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.5.1.3 1.5.1.3] </span></td></tr>
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Dihydrofolate_reductase Dihydrofolate reductase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.5.1.3 1.5.1.3] </span></td></tr>
<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2w3a FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2w3a OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2w3a RCSB], [http://www.ebi.ac.uk/pdbsum/2w3a PDBsum]</span></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=2w3a FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2w3a OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2w3a RCSB], [http://www.ebi.ac.uk/pdbsum/2w3a PDBsum]</span></td></tr>
<table>
</table>
== Disease ==
== Disease ==
[[http://www.uniprot.org/uniprot/DYR_HUMAN DYR_HUMAN]] Defects in DHFR are the cause of megaloblastic anemia due to dihydrofolate reductase deficiency (DHFRD) [MIM:[http://omim.org/entry/613839 613839]]. DHFRD is an inborn error of metabolism, characterized by megaloblastic anemia and/or pancytopenia, severe cerebral folate deficiency, and cerebral tetrahydrobiopterin deficiency. Clinical features include variable neurologic symptoms, ranging from severe developmental delay and generalized seizures in infancy, to childhood absence epilepsy with learning difficulties, to lack of symptoms.<ref>PMID:21310276</ref> <ref>PMID:21310277</ref>   
[[http://www.uniprot.org/uniprot/DYR_HUMAN DYR_HUMAN]] Defects in DHFR are the cause of megaloblastic anemia due to dihydrofolate reductase deficiency (DHFRD) [MIM:[http://omim.org/entry/613839 613839]]. DHFRD is an inborn error of metabolism, characterized by megaloblastic anemia and/or pancytopenia, severe cerebral folate deficiency, and cerebral tetrahydrobiopterin deficiency. Clinical features include variable neurologic symptoms, ranging from severe developmental delay and generalized seizures in infancy, to childhood absence epilepsy with learning difficulties, to lack of symptoms.<ref>PMID:21310276</ref> <ref>PMID:21310277</ref>   
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[[Category: Dihydrofolate reductase]]
[[Category: Dihydrofolate reductase]]
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Borhani, D W.]]
[[Category: Borhani, D W]]
[[Category: Leung, A K.W.]]
[[Category: Leung, A K.W]]
[[Category: Reynolds, R C.]]
[[Category: Reynolds, R C]]
[[Category: Lipophilic antifolate]]
[[Category: Lipophilic antifolate]]
[[Category: Nadp]]
[[Category: Nadp]]

Revision as of 21:31, 19 January 2015

HUMAN DIHYDROFOLATE REDUCTASE COMPLEXED WITH NADPH AND TRIMETHOPRIMHUMAN DIHYDROFOLATE REDUCTASE COMPLEXED WITH NADPH AND TRIMETHOPRIM

Structural highlights

2w3a 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.
Ligands:, , ,
Activity:Dihydrofolate reductase, with EC number 1.5.1.3
Resources:FirstGlance, OCA, RCSB, PDBsum

Disease

[DYR_HUMAN] Defects in DHFR are the cause of megaloblastic anemia due to dihydrofolate reductase deficiency (DHFRD) [MIM:613839]. DHFRD is an inborn error of metabolism, characterized by megaloblastic anemia and/or pancytopenia, severe cerebral folate deficiency, and cerebral tetrahydrobiopterin deficiency. Clinical features include variable neurologic symptoms, ranging from severe developmental delay and generalized seizures in infancy, to childhood absence epilepsy with learning difficulties, to lack of symptoms.[1] [2]

Function

[DYR_HUMAN] Key enzyme in folate metabolism. Contributes to the de novo mitochondrial thymidylate biosynthesis pathway. Catalyzes an essential reaction for de novo glycine and purine synthesis, and for DNA precursor synthesis. Binds its own mRNA and that of DHFRL1.[3] [4]

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. ↑ Banka S, Blom HJ, Walter J, Aziz M, Urquhart J, Clouthier CM, Rice GI, de Brouwer AP, Hilton E, Vassallo G, Will A, Smith DE, Smulders YM, Wevers RA, Steinfeld R, Heales S, Crow YJ, Pelletier JN, Jones S, Newman WG. Identification and characterization of an inborn error of metabolism caused by dihydrofolate reductase deficiency. Am J Hum Genet. 2011 Feb 11;88(2):216-25. doi: 10.1016/j.ajhg.2011.01.004. PMID:21310276 doi:10.1016/j.ajhg.2011.01.004
  2. ↑ Cario H, Smith DE, Blom H, Blau N, Bode H, Holzmann K, Pannicke U, Hopfner KP, Rump EM, Ayric Z, Kohne E, Debatin KM, Smulders Y, Schwarz K. Dihydrofolate reductase deficiency due to a homozygous DHFR mutation causes megaloblastic anemia and cerebral folate deficiency leading to severe neurologic disease. Am J Hum Genet. 2011 Feb 11;88(2):226-31. doi: 10.1016/j.ajhg.2011.01.007. PMID:21310277 doi:10.1016/j.ajhg.2011.01.007
  3. ↑ Anderson DD, Quintero CM, Stover PJ. Identification of a de novo thymidylate biosynthesis pathway in mammalian mitochondria. Proc Natl Acad Sci U S A. 2011 Sep 13;108(37):15163-8. doi:, 10.1073/pnas.1103623108. Epub 2011 Aug 26. PMID:21876188 doi:10.1073/pnas.1103623108
  4. ↑ Klon AE, Heroux A, Ross LJ, Pathak V, Johnson CA, Piper JR, Borhani DW. Atomic structures of human dihydrofolate reductase complexed with NADPH and two lipophilic antifolates at 1.09 a and 1.05 a resolution. J Mol Biol. 2002 Jul 12;320(3):677-93. PMID:12096917

2w3a, resolution 1.50Å

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