Pteridine reductase

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<StructureSection load='1mxh' size='350' side='right' caption='Structure of pteridine reductase complex with NADPH and folate(PDB entry [[1mxh]])' scene=''>
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<StructureSection load='' size='350' side='right' caption='Structure of pteridine reductase complex with NADPH, tetrahydrobiopterin, ethanediol and ethylene glycol (PDB entry [[2bfp]])' scene='54/547078/Cv/1'>
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== Function ==
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'''Pteridine reductase''' (PTR) catalyzes the reduction of 5,6,7,8-tetrahydrobiopterin (THBP) to biopterin. PTR is part of pterin and folate metabolism<ref>PMID:12651944</ref>. NADP is the hydrogen acceptor in this reduction.
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'''Pteridine reductase''' (PTR) catalyzes the reduction of 5,6,7,8-tetrahydrobiopterin (THBP) to biopterin. PTR is part of pterin and folate metabolism. NADP is the hydrogen acceptor in this reduction. PTR is essential for growth of trypanosomatid protozoans like Leishmania parasites, thus PTR inhibitors like methotrexate (MTX) or triaminoquinazoline (TAQ) are tested as potential drugs.
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== Relevance ==
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PTR is essential for growth of trypanosomatid protozoans like Leishmania parasites, thus PTR inhibitors like methotrexate (MTX) or triaminoquinazoline (TAQ) are tested as potential drugs<ref>PMID:18245389</ref>.
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== Structural highlights ==
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<scene name='54/547078/Cv/3'>Six residues (colored in deepskyblue) are important for creating the active site, substrate binding or implicated in catalysis</scene><ref>PMID:16055151</ref>. Water molecules are shown as red spheres.
</StructureSection>
</StructureSection>
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**[[1e7w]] – LmPTR1 + NADPH + MTX <BR />
**[[1e7w]] – LmPTR1 + NADPH + MTX <BR />
**[[1w0c]] – LmPTR1 + NADPH + TAQ <BR />
**[[1w0c]] – LmPTR1 + NADPH + TAQ <BR />
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**[[2bfa]], [[2bfm]], [[3h4v]], [[5l42]], [[5l4n]], [[6rxc]] – LmPTR1 + NADPH + inhibitor <BR />
**[[1p33]] – PTR1 + NADPH + MTX – ''Leishmania tarentolae''<BR />
**[[1p33]] – PTR1 + NADPH + MTX – ''Leishmania tarentolae''<BR />
**[[1mxf]] – TcPTR2 + NADPH + MTX – ''Trypanosoma cruzi''<BR />
**[[1mxf]] – TcPTR2 + NADPH + MTX – ''Trypanosoma cruzi''<BR />
**[[2c7v]] – TbPTR1 + NADPH + MTX – ''Trypanosoma brucei''<BR />
**[[2c7v]] – TbPTR1 + NADPH + MTX – ''Trypanosoma brucei''<BR />
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**[[3bmn]], [[3bmo]], [[3bmq]], [[2wd7]], [[2wd8]], [[2vz0]], [[3jq6]], [[3jq7]], [[3jq8]], [[3jq9]], [[3jqa]], [[3jqb]], [[3jqc]], [[3jqf]], [[3jqd]], [[3jqe]], [[3jqg]], [[3gn1]], [[3gn2]], [[3mcv]], [[2x9g]], [[2x9v]], [[2x9n]], [[2yhi]], [[2yhu]], [[4cl8]], [[4cld]], [[4cle]], [[4clh]], [[4clo]], [[4clr]], [[4clx]], [[4cm1]], [[4cm3]], [[4cm4]], [[4cm5]], [[4cm6]], [[4cm7]], [[4cm8]], [[4cm9]], [[4cma]], [[4cmb]], [[4cmc]], [[4cme]], [[4cmg]], [[4cmi]], [[4cmj]], [[4cmk]] – TbPTR1 + NADPH + inhibitor <BR />
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**[[3bmn]], [[3bmo]], [[3bmq]], [[2wd7]], [[2wd8]], [[2vz0]], [[3jq6]], [[3jq7]], [[3jq8]], [[3jq9]], [[3jqa]], [[3jqb]], [[3jqc]], [[3jqf]], [[3jqd]], [[3jqe]], [[3jqg]], [[3gn1]], [[3gn2]], [[3mcv]], [[2x9g]], [[2x9v]], [[2x9n]], [[2yhi]], [[2yhu]], [[4cl8]], [[4cld]], [[4cle]], [[4clh]], [[4clo]], [[4clr]], [[4clx]], [[4cm1]], [[4cm3]], [[4cm4]], [[4cm5]], [[4cm6]], [[4cm7]], [[4cm8]], [[4cm9]], [[4cma]], [[4cmb]], [[4cmc]], [[4cme]], [[4cmg]], [[4cmi]], [[4cmj]], [[4cmk]], [[5k6a]], [[5izc]], [[5jcj]], [[5jcx]], [[5jdc]], [[5jdi]], [[4wcd]], [[4wcf]], [[6gck]], [[6gcl]], [[6gcp]], [[6gcq]], [[6gd0]], [[6gd4]], [[6gdo]], [[6gdp]], [[6gex]], [[6gey]], [[6tbx]], [[6rx6]], [[6rx5]], [[6rx0]], [[7opj]] – TbPTR1 + NADPH + inhibitor <BR />
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**[[2bfa]], [[2bfm]], [[3h4v]] – LmPTR1 + NADPH + inhibitor <BR />
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**[[6hnc]], [[6hnr]], [[6how]] – TbPTR1 + NADPH + cycloguanyl derivative<BR />
*Pteridine reductase complex with ligand
*Pteridine reductase complex with ligand
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**[[2qhx]] – LmPTR1 + NADPH + ligand<BR />
**[[2qhx]] – LmPTR1 + NADPH + ligand<BR />
**[[1e92]], [[2bf7]] – LmPTR1 + NADPH + DHBP <BR />
**[[1e92]], [[2bf7]] – LmPTR1 + NADPH + DHBP <BR />
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**[[7pxx]] – LmPTR1 + NADPH + folate<BR />
**[[1mxh]] – TcPTR1 + NADPH + folate <BR />
**[[1mxh]] – TcPTR1 + NADPH + folate <BR />
**[[3bmc]] – TbPTR1 + NADPH + folate <BR />
**[[3bmc]] – TbPTR1 + NADPH + folate <BR />
}}
}}
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== References ==
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<references/>
[[Category:Topic Page]]
[[Category:Topic Page]]

Current revision

Structure of pteridine reductase complex with NADPH, tetrahydrobiopterin, ethanediol and ethylene glycol (PDB entry 2bfp)

Drag the structure with the mouse to rotate

3D structures of pteridine reductase

Updated on 03-October-2023

References

  1. ↑ Bransteitter R, Pham P, Scharff MD, Goodman MF. Activation-induced cytidine deaminase deaminates deoxycytidine on single-stranded DNA but requires the action of RNase. Proc Natl Acad Sci U S A. 2003 Apr 1;100(7):4102-7. Epub 2003 Mar 21. PMID:12651944 doi:http://dx.doi.org/10.1073/pnas.0730835100
  2. ↑ Cavazzuti A, Paglietti G, Hunter WN, Gamarro F, Piras S, Loriga M, Allecca S, Corona P, McLuskey K, Tulloch L, Gibellini F, Ferrari S, Costi MP. Discovery of potent pteridine reductase inhibitors to guide antiparasite drug development. Proc Natl Acad Sci U S A. 2008 Feb 5;105(5):1448-53. Epub 2008 Feb 1. PMID:18245389
  3. ↑ Schuttelkopf AW, Hardy LW, Beverley SM, Hunter WN. Structures of Leishmania major pteridine reductase complexes reveal the active site features important for ligand binding and to guide inhibitor design. J Mol Biol. 2005 Sep 9;352(1):105-16. PMID:16055151 doi:http://dx.doi.org/10.1016/j.jmb.2005.06.076

Proteopedia Page Contributors and Editors (what is this?)

Michal Harel, Alexander Berchansky, Joel L. Sussman

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