1b5t: Difference between revisions
New page: left|200px<br /><applet load="1b5t" size="450" color="white" frame="true" align="right" spinBox="true" caption="1b5t, resolution 2.50Å" /> '''ESCHERICHIA COLI MET... |
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[[Image:1b5t.gif|left|200px]]<br /><applet load="1b5t" size=" | [[Image:1b5t.gif|left|200px]]<br /><applet load="1b5t" size="350" color="white" frame="true" align="right" spinBox="true" | ||
caption="1b5t, resolution 2.50Å" /> | caption="1b5t, resolution 2.50Å" /> | ||
'''ESCHERICHIA COLI METHYLENETETRAHYDROFOLATE REDUCTASE'''<br /> | '''ESCHERICHIA COLI METHYLENETETRAHYDROFOLATE REDUCTASE'''<br /> | ||
==Overview== | ==Overview== | ||
Elevated plasma homocysteine levels are associated with increased risk for | Elevated plasma homocysteine levels are associated with increased risk for cardiovascular disease and neural tube defects in humans. Folate treatment decreases homocysteine levels and dramatically reduces the incidence of neural tube defects. The flavoprotein methylenetetrahydrofolate reductase (MTHFR) is a likely target for these actions of folate. The most common genetic cause of mildly elevated plasma homocysteine in humans is the MTHFR polymorphism A222V (base change C677-->T). The X-ray analysis of E. coli MTHFR, reported here, provides a model for the catalytic domain that is shared by all MTHFRs. This domain is a beta8alpha8 barrel that binds FAD in a novel fashion. Ala 177, corresponding to Ala 222 in human MTHFR, is near the bottom of the barrel and distant from the FAD. The mutation A177V does not affect Km or k(cat) but instead increases the propensity for bacterial MTHFR to lose its essential flavin cofactor. Folate derivatives protect wild-type and mutant E. coli enzymes against flavin loss, and protect human MTHFR and the A222V mutant against thermal inactivation, suggesting a mechanism by which folate treatment reduces homocysteine levels. | ||
==About this Structure== | ==About this Structure== | ||
1B5T is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli] with HG and FAD as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Deleted_entry Deleted entry], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.7.99.5 1.7.99.5] Full crystallographic information is available from [http:// | 1B5T is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli] with <scene name='pdbligand=HG:'>HG</scene> and <scene name='pdbligand=FAD:'>FAD</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Deleted_entry Deleted entry], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.7.99.5 1.7.99.5] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1B5T OCA]. | ||
==Reference== | ==Reference== | ||
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[[Category: Escherichia coli]] | [[Category: Escherichia coli]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Guenther, B | [[Category: Guenther, B D.]] | ||
[[Category: Ludwig, M | [[Category: Ludwig, M L.]] | ||
[[Category: Matthews, R | [[Category: Matthews, R G.]] | ||
[[Category: Rozen, R.]] | [[Category: Rozen, R.]] | ||
[[Category: Sheppard, C | [[Category: Sheppard, C A.]] | ||
[[Category: Tran, P.]] | [[Category: Tran, P.]] | ||
[[Category: FAD]] | [[Category: FAD]] | ||
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[[Category: reductase]] | [[Category: reductase]] | ||
''Page seeded by [http:// | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 11:51:49 2008'' | ||
Revision as of 12:51, 21 February 2008
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ESCHERICHIA COLI METHYLENETETRAHYDROFOLATE REDUCTASE
OverviewOverview
Elevated plasma homocysteine levels are associated with increased risk for cardiovascular disease and neural tube defects in humans. Folate treatment decreases homocysteine levels and dramatically reduces the incidence of neural tube defects. The flavoprotein methylenetetrahydrofolate reductase (MTHFR) is a likely target for these actions of folate. The most common genetic cause of mildly elevated plasma homocysteine in humans is the MTHFR polymorphism A222V (base change C677-->T). The X-ray analysis of E. coli MTHFR, reported here, provides a model for the catalytic domain that is shared by all MTHFRs. This domain is a beta8alpha8 barrel that binds FAD in a novel fashion. Ala 177, corresponding to Ala 222 in human MTHFR, is near the bottom of the barrel and distant from the FAD. The mutation A177V does not affect Km or k(cat) but instead increases the propensity for bacterial MTHFR to lose its essential flavin cofactor. Folate derivatives protect wild-type and mutant E. coli enzymes against flavin loss, and protect human MTHFR and the A222V mutant against thermal inactivation, suggesting a mechanism by which folate treatment reduces homocysteine levels.
About this StructureAbout this Structure
1B5T is a Single protein structure of sequence from Escherichia coli with and as ligands. Active as Deleted entry, with EC number 1.7.99.5 Full crystallographic information is available from OCA.
ReferenceReference
The structure and properties of methylenetetrahydrofolate reductase from Escherichia coli suggest how folate ameliorates human hyperhomocysteinemia., Guenther BD, Sheppard CA, Tran P, Rozen R, Matthews RG, Ludwig ML, Nat Struct Biol. 1999 Apr;6(4):359-65. PMID:10201405
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