7F3Y

Wild-type Plasmodium falciparum dihydrofolate reductase-thymidylate synthase (PfDHFR-TS) complexed with methotrexate (MTX), NADPH and dUMP

Summary for 7F3Y

• Entry DOI: 10.2210/pdb7f3y/pdb
• Descriptor: Bifunctional dihydrofolate reductase-thymidylate synthase, NADPH DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE, METHOTREXATE, ... (6 entities in total)
• Functional Keywords: pfdhfr, methotrexate, dihydrofolate reductase, plasmodium falciparum, structural protein
• Biological source: Plasmodium falciparum (malaria parasite P. falciparum)
• Total number of polymer chains: 2
• Total formula weight: 147310.71

Authors

Vanichtanankul, J.,Tanramluk, D.,Yuvaniyama, J.,Yuthavong, Y. (deposition date: 2021-06-17, release date: 2021-09-22, Last modification date: 2023-11-29)

Primary citation

Tanramluk, D.,Pakotiprapha, D.,Phoochaijaroen, S.,Chantravisut, P.,Thampradid, S.,Vanichtanankul, J.,Narupiyakul, L.,Akavipat, R.,Yuvaniyama, J.
MANORAA: A machine learning platform to guide protein-ligand design by anchors and influential distances.
Structure, 30:181-189.e5, 2022

PubMed Abstract: The MANORAA platform uses structure-based approaches to provide information on drug design originally derived from mapping tens of thousands of amino acids on a grid. In-depth analyses of the pockets, frequently occurring atoms, influential distances, and active-site boundaries are used for the analysis of active sites. The algorithms derived provide model equations that can predict whether changes in distances, such as contraction or expansion, will result in improved binding affinity. The algorithm is confirmed using kinetic studies of dihydrofolate reductase (DHFR), together with two DHFR-TS crystal structures. Empirical analyses of 881 crystal structures involving 180 ligands are used to interpret protein-ligand binding affinities. MANORAA links to major biological databases for web-based analysis of drug design. The frequency of atoms inside the main protease structures, including those from SARS-CoV-2, shows how the rigid part of the ligand can be used as a probe for molecular design (http://manoraa.org).

PubMed: 34614393
DOI: 10.1016/j.str.2021.09.004

Experimental method

X-RAY DIFFRACTION (2.252 Å)