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| | <StructureSection load='1e92' size='340' side='right'caption='[[1e92]], [[Resolution|resolution]] 2.20Å' scene=''> | | <StructureSection load='1e92' size='340' side='right'caption='[[1e92]], [[Resolution|resolution]] 2.20Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[1e92]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Leima Leima]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1E92 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=1E92 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[1e92]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Leishmania_major Leishmania major]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1E92 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1E92 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=HBI:7,8-DIHYDROBIOPTERIN'>HBI</scene>, <scene name='pdbligand=NAP:NADP+NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NAP</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='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1e7w|1e7w]]</div></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=HBI:7,8-DIHYDROBIOPTERIN'>HBI</scene>, <scene name='pdbligand=NAP:NADP+NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NAP</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PTR1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=5664 LEIMA])</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=1e92 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1e92 OCA], [https://pdbe.org/1e92 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1e92 RCSB], [https://www.ebi.ac.uk/pdbsum/1e92 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1e92 ProSAT]</span></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Pteridine_reductase Pteridine reductase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.5.1.33 1.5.1.33] </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=1e92 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1e92 OCA], [http://pdbe.org/1e92 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1e92 RCSB], [http://www.ebi.ac.uk/pdbsum/1e92 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1e92 ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/PTR1_LEIMA PTR1_LEIMA] Exhibits a NADPH-dependent biopterin reductase activity. Has good activity with folate and significant activity with dihydrofolate and dihydrobiopterin, but not with quinonoid dihydrobiopterin. Confers resistance to methotrexate (MTX).<ref>PMID:7972081</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Leima]] | + | [[Category: Leishmania major]] |
| - | [[Category: Pteridine reductase]]
| + | [[Category: Hunter WN]] |
| - | [[Category: Hunter, W N]] | + | [[Category: Schuettelkopf AW]] |
| - | [[Category: Schuettelkopf, A W]] | + | |
| - | [[Category: Drug resistance]]
| + | |
| - | [[Category: Pterin salvage]]
| + | |
| - | [[Category: Short-chain dehydrogenase/reductase]]
| + | |
| - | [[Category: Trypanosomatid]]
| + | |
| Structural highlights
Function
PTR1_LEIMA Exhibits a NADPH-dependent biopterin reductase activity. Has good activity with folate and significant activity with dihydrofolate and dihydrobiopterin, but not with quinonoid dihydrobiopterin. Confers resistance to methotrexate (MTX).[1]
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
Pteridine reductase (PTR1) is a short-chain reductase (SDR) responsible for the salvage of pterins in parasitic trypanosomatids. PTR1 catalyzes the NADPH-dependent two-step reduction of oxidized pterins to the active tetrahydro-forms and reduces susceptibility to antifolates by alleviating dihydrofolate reductase (DHFR) inhibition. Crystal structures of PTR1 complexed with cofactor and 7,8-dihydrobiopterin (DHB) or methotrexate (MTX) delineate the enzyme mechanism, broad spectrum of activity and inhibition by substrate or an antifolate. PTR1 applies two distinct reductive mechanisms to substrates bound in one orientation. The first reduction uses the generic SDR mechanism, whereas the second shares similarities with the mechanism proposed for DHFR. Both DHB and MTX form extensive hydrogen bonding networks with NADP(H) but differ in the orientation of the pteridine.
Pteridine reductase mechanism correlates pterin metabolism with drug resistance in trypanosomatid parasites.,Gourley DG, Schuttelkopf AW, Leonard GA, Luba J, Hardy LW, Beverley SM, Hunter WN Nat Struct Biol. 2001 Jun;8(6):521-5. PMID:11373620[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Bello AR, Nare B, Freedman D, Hardy L, Beverley SM. PTR1: a reductase mediating salvage of oxidized pteridines and methotrexate resistance in the protozoan parasite Leishmania major. Proc Natl Acad Sci U S A. 1994 Nov 22;91(24):11442-6. PMID:7972081
- ↑ Gourley DG, Schuttelkopf AW, Leonard GA, Luba J, Hardy LW, Beverley SM, Hunter WN. Pteridine reductase mechanism correlates pterin metabolism with drug resistance in trypanosomatid parasites. Nat Struct Biol. 2001 Jun;8(6):521-5. PMID:11373620 doi:10.1038/88584
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