1jbv: Difference between revisions
New page: left|200px<br /><applet load="1jbv" size="450" color="white" frame="true" align="right" spinBox="true" caption="1jbv, resolution 1.95Å" /> '''FPGS-AMPPCP complex'... |
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[[Image:1jbv.jpg|left|200px]]<br /><applet load="1jbv" size=" | [[Image:1jbv.jpg|left|200px]]<br /><applet load="1jbv" size="350" color="white" frame="true" align="right" spinBox="true" | ||
caption="1jbv, resolution 1.95Å" /> | caption="1jbv, resolution 1.95Å" /> | ||
'''FPGS-AMPPCP complex'''<br /> | '''FPGS-AMPPCP complex'''<br /> | ||
==Overview== | ==Overview== | ||
Folic acid is an essential vitamin for normal cell growth, primarily | Folic acid is an essential vitamin for normal cell growth, primarily through its central role in one-carbon metabolism. Folate analogs (antifolates) are targeted at the same reactions and are widely used as therapeutic drugs for cancer and bacterial infections. Effective retention of folates in cells and the efficacy of antifolate drugs both depend upon the addition of a polyglutamate tail to the folate or antifolate molecule by the enzyme folylpolyglutamate synthetase (FPGS). The reaction mechanism involves the ATP-dependent activation of the free carboxylate group on the folate molecule to give an acyl phosphate intermediate, followed by attack by the incoming L-glutamate substrate. FPGS shares a number of structural and mechanistic details with the bacterial cell wall ligases MurD, MurE and MurF, and these enzymes, along with FPGS, form a subfamily of the ADP-forming amide bond ligase family. High-resolution crystallographic analyses of binary and ternary complexes of Lactobacillus casei FPGS reveal that binding of the first substrate (ATP) is not sufficient to generate an active enzyme. However, binding of folate as the second substrate triggers a large conformational change that activates FPGS and allows the enzyme to adopt a form that is then able to bind the third substrate, L-glutamate, and effect the addition of a polyglutamate tail to the folate. | ||
==About this Structure== | ==About this Structure== | ||
1JBV is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Lactobacillus_casei Lactobacillus casei] with MG and ACP as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Tetrahydrofolate_synthase Tetrahydrofolate synthase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=6.3.2.17 6.3.2.17] Full crystallographic information is available from [http:// | 1JBV is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Lactobacillus_casei Lactobacillus casei] with <scene name='pdbligand=MG:'>MG</scene> and <scene name='pdbligand=ACP:'>ACP</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Tetrahydrofolate_synthase Tetrahydrofolate synthase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=6.3.2.17 6.3.2.17] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1JBV OCA]. | ||
==Reference== | ==Reference== | ||
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[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Tetrahydrofolate synthase]] | [[Category: Tetrahydrofolate synthase]] | ||
[[Category: Baker, E | [[Category: Baker, E N.]] | ||
[[Category: Bognar, A | [[Category: Bognar, A L.]] | ||
[[Category: Cross, J | [[Category: Cross, J A.]] | ||
[[Category: Smith, C | [[Category: Smith, C A.]] | ||
[[Category: Sun, X.]] | [[Category: Sun, X.]] | ||
[[Category: ACP]] | [[Category: ACP]] | ||
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[[Category: fpgs amppcp complex]] | [[Category: fpgs amppcp complex]] | ||
''Page seeded by [http:// | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:20:53 2008'' | ||
Revision as of 14:20, 21 February 2008
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FPGS-AMPPCP complex
OverviewOverview
Folic acid is an essential vitamin for normal cell growth, primarily through its central role in one-carbon metabolism. Folate analogs (antifolates) are targeted at the same reactions and are widely used as therapeutic drugs for cancer and bacterial infections. Effective retention of folates in cells and the efficacy of antifolate drugs both depend upon the addition of a polyglutamate tail to the folate or antifolate molecule by the enzyme folylpolyglutamate synthetase (FPGS). The reaction mechanism involves the ATP-dependent activation of the free carboxylate group on the folate molecule to give an acyl phosphate intermediate, followed by attack by the incoming L-glutamate substrate. FPGS shares a number of structural and mechanistic details with the bacterial cell wall ligases MurD, MurE and MurF, and these enzymes, along with FPGS, form a subfamily of the ADP-forming amide bond ligase family. High-resolution crystallographic analyses of binary and ternary complexes of Lactobacillus casei FPGS reveal that binding of the first substrate (ATP) is not sufficient to generate an active enzyme. However, binding of folate as the second substrate triggers a large conformational change that activates FPGS and allows the enzyme to adopt a form that is then able to bind the third substrate, L-glutamate, and effect the addition of a polyglutamate tail to the folate.
About this StructureAbout this Structure
1JBV is a Single protein structure of sequence from Lactobacillus casei with and as ligands. Active as Tetrahydrofolate synthase, with EC number 6.3.2.17 Full crystallographic information is available from OCA.
ReferenceReference
Folate-binding triggers the activation of folylpolyglutamate synthetase., Sun X, Cross JA, Bognar AL, Baker EN, Smith CA, J Mol Biol. 2001 Jul 27;310(5):1067-78. PMID:11501996
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