1MXH

Crystal Structure of Substrate Complex of Putative Pteridine Reductase 2 (PTR2) from Trypanosoma cruzi

Summary for 1MXH

• Entry DOI: 10.2210/pdb1mxh/pdb
• Related: 1E7W 1E92 1MXF
• Descriptor: PTERIDINE REDUCTASE 2, NADP NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE, DIHYDROFOLIC ACID, ... (4 entities in total)
• Functional Keywords: sdr topology, protein-substrate complex, oxidoreductase
• Biological source: Trypanosoma cruzi
• Total number of polymer chains: 4
• Total formula weight: 121472.38

Authors

Schormann, N.,Pal, B.,Senkovich, O.,Carson, M.,Howard, A.,Smith, C.,Delucas, L.,Chattopadhyay, D. (deposition date: 2002-10-02, release date: 2003-10-14, Last modification date: 2024-02-14)

Primary citation

Schormann, N.,Pal, B.,Senkovich, O.,Carson, M.,Howard, A.,Smith, C.,Delucas, L.,Chattopadhyay, D.
Crystal structure of Trypanosoma cruzi pteridine reductase 2 in complex with a substrate and an inhibitor.
J.Struct.Biol., 152:64-75, 2005

PubMed Abstract: Reduced pteridines are required for a number of important cellular functions. Trypanosomatid parasites, unlike their mammalian hosts, are pteridine auxotrophs and salvage the precursor pteridines from the host and reduce them to the respective biologically active tetrahydro forms using parasite-encoded enzymes. These enzymes may offer selective drug targets. In Leishmania, pteridine reductase 1 (PTR1), the primary enzyme for reducing pterins, is also responsible for resistance to antifolate drugs. Typically, PTR1 is more active with fully oxidized biopterin and folate than with their reduced counterparts. We have identified an enzyme, TcPTR2 of Trypanosoma cruzi, which though very similar to PTR1 in its primary sequence, can reduce only dihydrobiopterin and dihydrofolate and not oxidized pteridines. The structures of an inhibitor (methotrexate) and a substrate (dihydrofolate) complex of this enzyme demonstrate that the orientation of the substrate and the inhibitor in the active site of TcPTR2 are different from each other. However, the orientation of each ligand is similar to that of the corresponding ligand in Leishmania major PTR1 complexes.

PubMed: 16168672
DOI: 10.1016/j.jsb.2005.07.008

Experimental method

X-RAY DIFFRACTION (2.2 Å)