Crystal structure of human folate receptor alpha in complex with novel antifolate AGF183

Summary for 5IZQ

DescriptorFolate receptor alpha, N-(4-{[2-(2-amino-4-oxo-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidin-6-yl)ethyl]amino}benzene-1-carbonyl)-L-glutamic acid (2 entities in total)
Functional Keywordsfolate receptor alpha, antifolate, tumor targeting, 2-amino-4-oxo-6-substituted pyrrolo[2, 3-d]pyrimidine, signaling protein
Biological sourceHomo sapiens (Human)
Cellular locationCell membrane; Lipid-anchor, GPI-anchor P15328
Total number of polymer chains8
Total molecular weight224821.16
Ke, J.,Gu, X.,Brunzelle, J.S.,Xu, H.E.,Melcher, K. (deposition date: 2016-03-25, release date: 2016-08-10, Last modification date: 2017-11-01)
Primary citation
Golani, L.K.,Wallace-Povirk, A.,Deis, S.M.,Wong, J.,Ke, J.,Gu, X.,Raghavan, S.,Wilson, M.R.,Li, X.,Polin, L.,de Waal, P.W.,White, K.,Kushner, J.,O'Connor, C.,Hou, Z.,Xu, H.E.,Melcher, K.,Dann, C.E.,Matherly, L.H.,Gangjee, A.
Tumor Targeting with Novel 6-Substituted Pyrrolo [2,3-d] Pyrimidine Antifolates with Heteroatom Bridge Substitutions via Cellular Uptake by Folate Receptor alpha and the Proton-Coupled Folate Transporter and Inhibition of de Novo Purine Nucleotide Biosynthesis.
J.Med.Chem., 59:7856-7876, 2016
PubMed: 27458733 (PDB entries with the same primary citation)
DOI: 10.1021/acs.jmedchem.6b00594
MImport into Mendeley
Experimental method

Structure validation

RfreeClashscoreRamachandran outliersSidechain outliersRSRZ outliers0.25970.5%4.1%1.8%MetricValuePercentile RanksWorseBetterPercentile relative to all X-ray structuresPercentile relative to X-ray structures of similar resolution