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| <StructureSection load='2bfp' 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'> | | <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 == | | == Function == |
Revision as of 14:11, 23 September 2017
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Function
Pteridine reductase (PTR) catalyzes the reduction of 5,6,7,8-tetrahydrobiopterin (THBP) to biopterin. PTR is part of pterin and folate metabolism[1]. NADP is the hydrogen acceptor in this reduction.
Relevance
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[2].
Structural highlights
Six residues (colored in deepskyblue) are important for creating the active site, substrate binding or implicated in catalysis[3]. Water molecules shown as red spheres.
- ↑ 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:https://dx.doi.org/10.1073/pnas.0730835100
- ↑ 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
- ↑ 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:https://dx.doi.org/10.1016/j.jmb.2005.06.076
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3D structures of pteridine reductase
Updated on 23-September-2017
{"openlevels":0}
- Pteridine reductase
- 2xox – LdPTR1 (mutant) – Leishmania donovani
- 2bfo – LmPTR1 + NADPH – Leishmania major
- Pteridine reductase complex with inhibitor
- 1e7w – LmPTR1 + NADPH + MTX
- 1w0c – LmPTR1 + NADPH + TAQ
- 1p33 – PTR1 + NADPH + MTX – Leishmania tarentolae
- 1mxf – TcPTR2 + NADPH + MTX – Trypanosoma cruzi
- 2c7v – TbPTR1 + NADPH + MTX – Trypanosoma brucei
- 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 – TbPTR1 + NADPH + inhibitor
- 2bfa, 2bfm, 3h4v, 5l42, 5l4n – LmPTR1 + NADPH + inhibitor
- Pteridine reductase complex with ligand
- 2bfp – LmPTR1 + NADPH + THBP
- 2qhx – LmPTR1 + NADPH + ligand
- 1e92, 2bf7 – LmPTR1 + NADPH + DHBP
- 1mxh – TcPTR1 + NADPH + folate
- 3bmc – TbPTR1 + NADPH + folate
References
