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| | <StructureSection load='1zlx' size='340' side='right'caption='[[1zlx]], [[Resolution|resolution]] 2.20Å' scene=''> | | <StructureSection load='1zlx' size='340' side='right'caption='[[1zlx]], [[Resolution|resolution]] 2.20Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[1zlx]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1ZLX OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=1ZLX FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[1zlx]] is a 1 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=1ZLX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1ZLX FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</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]] 2.2Å</td></tr> |
| - | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene></td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1meo|1meo]], [[1mej|1mej]], [[1men|1men]], [[1njs|1njs]]</div></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=1zlx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1zlx OCA], [https://pdbe.org/1zlx PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1zlx RCSB], [https://www.ebi.ac.uk/pdbsum/1zlx PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1zlx ProSAT]</span></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">GART, PRGS ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
| + | |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[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] </span></td></tr>
| + | |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=1zlx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1zlx OCA], [http://pdbe.org/1zlx PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1zlx RCSB], [http://www.ebi.ac.uk/pdbsum/1zlx PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1zlx ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/PUR2_HUMAN PUR2_HUMAN] |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Phosphoribosylglycinamide formyltransferase]]
| + | [[Category: Caperelli CA]] |
| - | [[Category: Caperelli, C A]] | + | [[Category: Dahms TE]] |
| - | [[Category: Dahms, T E]] | + | [[Category: Giroux EL]] |
| - | [[Category: Giroux, E L]] | + | [[Category: Sainz G]] |
| - | [[Category: Sainz, G]] | + | [[Category: Smith JL]] |
| - | [[Category: Smith, J L]] | + | |
| - | [[Category: Folate binding loop]]
| + | |
| - | [[Category: Modified doubly wound alpha/beta sheet]]
| + | |
| - | [[Category: Phosphate binding loop]]
| + | |
| - | [[Category: Seven stranded beta-pleated sheet]]
| + | |
| - | [[Category: Transferase]]
| + | |
| Structural highlights
Function
PUR2_HUMAN
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
Glycinamide ribonucleotide transformylase (GART; 10-formyltetrahydrofolate:5'-phosphoribosylglycinamide formyltransferase, EC 2.1.2.2), an essential enzyme in de novo purine biosynthesis, has been a chemotherapeutic target for several decades. The three-dimensional structure of the GART domain from the human trifunctional enzyme has been solved by X-ray crystallography. Models of the apoenzyme, and a ternary complex with the 10-formyl-5,8-dideazafolate cosubstrate and a glycinamide ribonucleotide analogue, hydroxyacetamide ribonucleotide [alpha,beta-N-(hydroxyacetyl)-d-ribofuranosylamine], are reported to 2.2 and 2.07 A, respectively. The model of the apoenzyme represents the first structure of GART, from any source, with a completely unoccupied substrate and cosubstrate site, while the ternary complex is the first structure of the human GART domain that is bound at both the substrate and cosubstrate sites. A comparison of the two models therefore reveals subtle structural differences that reflect substrate and cosubstrate binding effects and implies roles for the invariant residues Gly 133, Gly 146, and His 137. Preactivation of the DDF formyl group appears to be key for catalysis, and structural flexibility of the active end of the substrate may facilitate nucleophilic attack. A change in pH, rather than folate binding, correlates with movement of the folate binding loop, whereas the phosphate binding loop position does not vary with pH. The electrostatic surface potentials of the human GART domain and Escherichia coli enzyme explain differences in the binding affinity of polyglutamylated folates, and these differences have implications to future chemotherapeutic agent design.
The apo and ternary complex structures of a chemotherapeutic target: human glycinamide ribonucleotide transformylase.,Dahms TE, Sainz G, Giroux EL, Caperelli CA, Smith JL Biochemistry. 2005 Jul 26;44(29):9841-50. PMID:16026156[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Dahms TE, Sainz G, Giroux EL, Caperelli CA, Smith JL. The apo and ternary complex structures of a chemotherapeutic target: human glycinamide ribonucleotide transformylase. Biochemistry. 2005 Jul 26;44(29):9841-50. PMID:16026156 doi:10.1021/bi050307g
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