1mej: Difference between revisions
New page: left|200px<br /> <applet load="1mej" size="450" color="white" frame="true" align="right" spinBox="true" caption="1mej, resolution 2.00Å" /> '''Human Glycinamide R... |
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'''Human Glycinamide Ribonucleotide Transformylase domain at pH 8.5'''<br /> | '''Human Glycinamide Ribonucleotide Transformylase domain at pH 8.5'''<br /> | ||
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==About this Structure== | ==About this Structure== | ||
1MEJ is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with PO4 and GOL as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Phosphoribosylglycinamide_formyltransferase Phosphoribosylglycinamide formyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.1.2.2 2.1.2.2] Full crystallographic information is available from [http:// | 1MEJ is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=PO4:'>PO4</scene> and <scene name='pdbligand=GOL:'>GOL</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Phosphoribosylglycinamide_formyltransferase Phosphoribosylglycinamide formyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.1.2.2 2.1.2.2] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1MEJ OCA]. | ||
==Reference== | ==Reference== | ||
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[[Category: purine biosynthesis]] | [[Category: purine biosynthesis]] | ||
''Page seeded by [http:// | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri Feb 15 16:23:38 2008'' | ||
Revision as of 17:23, 15 February 2008
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Human Glycinamide Ribonucleotide Transformylase domain at pH 8.5
OverviewOverview
Glycinamide ribonucleotide transformylase (GAR Tfase) is a key, folate-dependent enzyme in the de novo purine biosynthesis pathway and, as, such, has been the target for antitumor drug design. Here, we describe the, crystal structures of the human GAR Tfase (purN) component of the human, trifunctional protein (purD-purM-purN) at various pH values and in complex, with its substrate. Human GAR Tfase exhibits pH-dependent enzyme activity, with its maximum around pH 7.5-8. Comparison of unliganded human GAR Tfase, structures at pH 4.2 and pH 8.5 reveals conformational differences in the, substrate binding loop, which at pH 4.2 occupies the binding cleft and, prohibits substrate binding, while at pH 8.5 is permissive for substrate, binding. The crystal structure of GAR Tfase with its natural substrate, beta-glycinamide ribonucleotide (beta-GAR), at pH 8.5 confirms this, conformational isomerism. Surprisingly, several important structural, differences are found between human GAR Tfase and previously reported E., coli GAR Tfase structures, which have been used as the primary template, for drug design studies. While the E. coli structure gave valuable, insights into the active site and formyl transfer mechanism, differences, in structure and inhibition between the bacterial and mammalian enzymes, suggest that the human GAR Tfase structure is now the appropriate template, for the design of anti-cancer agents.
About this StructureAbout this Structure
1MEJ is a Single protein structure of sequence from Homo sapiens with and as ligands. Active as Phosphoribosylglycinamide formyltransferase, with EC number 2.1.2.2 Full crystallographic information is available from OCA.
ReferenceReference
Crystal structures of human GAR Tfase at low and high pH and with substrate beta-GAR., Zhang Y, Desharnais J, Greasley SE, Beardsley GP, Boger DL, Wilson IA, Biochemistry. 2002 Dec 3;41(48):14206-15. PMID:12450384
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