Human Dihydrofolate Reductase Complexed With NADPH and 2,4-Diamino-5-(1-o-carboranylmethyl)-6-methylpyrimidine, A novel boron containing, nonclassical Antifolate

NADPH DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE

Novel Boron-Containing, Nonclassical Antifolates: Synthesis and Preliminary Biological and Structural Evaluation.

VGSLNCIVAVSQNMGIGKNGDLPWPPLRNEFRYFQRMTTTSSVEGKQNLVIMGKKTWFSIPEKNRPLKGRINLVLSRELK
EPPQGAHFLSRSLDDALKLTEQPELANKVDMVWIVGGSSVYKEAMNHPGHLKLFVTRIMQDFESDTFFPEIDLEKYKLLP
EYPGVLSDVQEEKGIKYKFEVYEKND

INTENSITIES WERE CONVERTED TO STRUCTURE FACTORS USING CCP4 PROGRAM TRUNCATE.

THE TERNARY COMPLEX OF DHFR WITH NADPH AND 34B WAS FORMED BY MIXING HUMAN DHFR (20 MG/ML IN 25 MM KPO4 (PH 7.0), 0.1 MM EDTA, AND 3 MM NAN3) WITH 60 MM NADPH, FOLLOWED 15 MINUTES LATER BY 60 MM OF INHIBITOR IN DMSO (FINAL CONCENTRATIONS OF 2 MM NADPH AND 2 MM INHIBITOR). THIS COMPLEX SOLUTION WAS MIXED WITH AN EQUAL VOLUME OF PRECIPITANT CONTAINING 24-33% PEG 4000, 0.2 M LI2SO4, 0.1 M TRIS CL (PH 7.9-8.4), 5% GLYCEROL, AND EQUILIBRATED WITH THE PRECIPITANT BY HANGING DROP VAPOR DIFFUSION AT 277 K. THE CRYSTAL GREW IN ABOUT 3 WEEKS. THE CRYSTAL WAS FLASH-COOLED DIRECTLY IN LIQUID NITROGEN AFTER HARVESTING INTO MOTHER LIQUOR CONTAINING 10% GLYCEROL.

STRUCTURE-BASED DESIGN AND SYNTHESIS OF LIPOPHILIC 2,4- DIAMINO-6-SUBSTITUTED QUINAZOLINES AND THEIR EVALUATION AS INHIBITORS OF DIHYDROFOLATE REDUCTASE AND POTENTIAL ANTITUMOR AGENTS

DIHYDROFOLATE REDUCTASE (DHFR) COMPLEX WITH FOLATE

DIHYDROFOLATE REDUCTASE (DHFR) MUTANT WITH LEU 22 REPLACED BY PHE (L22F) COMPLEXED WITH NADPH AND PIRITREXIM (PTX)

DIHYDROFOLATE REDUCTASE (DHFR) MUTANT WITH LEU 22 REPLACED BY TYR (L22Y) COMPLEXED WITH NADPH AND METHOTREXATE

DIHYDROFOLATE REDUCTASE COMPLEX WITH FOLATE

COMPARISON OF TERNARY CRYSTAL COMPLEXES OF HUMAN DIHYDROFOLATE REDUCTASE WITH NADPH AND A CLASSICAL ANTITUMOR FUROPYRIMDINE

HUMAN DIHYDROFOLATE REDUCTASE COMPLEXED WITH NADPH AND 6-([5-QUINOLYLAMINO]METHYL)-2,4 -DIAMINO-5-METHYLPYRIDO[2,3-D]PYRIMIDINE ( SRI-9439), A LIPOPHILIC ANTIFOLATE

HUMAN DIHYDROFOLATE REDUCTASE COMPLEXED WITH NADPH AND (Z)-6-(2-[2,5-DIMETHOXYPHENYL] ETHEN-1-YL)-2,4-DIAMINO-5-METHYLPYRIDO[2 ,3-D]PYRIMIDINE (SRI-9662), A LIPOPHILICANTIFOLATE

ANALYSIS OF TWO POLYMORPHIC FORMS OF A PYRIDO[2,3-D]PYRIMIDINE N9-C10 REVERSE- BRIDGE ANTIFOLATE BINARYCOMPLEX WITH HUMAN DIHYDROFOLATE REDUCTASE

HUMAN DIHYDROFOLATE REDUCTASE, MONOCLINIC (P21 ) CRYSTAL FORM

HUMAN DIHYDROFOLATE REDUCTASE, ORTHORHOMBIC (P21 21 21) CRYSTAL FORM

ANALYSIS OF THREE CRYSTAL STRUCTURE DETERMINATIONS OF A 5-METHYL-6-N- METHYLANILINO PYRIDOPYRIMIDINE ANTIFOLATECOMPLEX WITH HUMAN DIHYDROFOLATE REDUCTASE

STRUCTURE DETERMINATION OF TETRAHYDROQUINAZOLINEANTIFOLATES IN COMPLEX WITH HUMAN AND PNEUMOCYSTIS CARINIIDIHYDROFOLATE REDUCTASE: CORRELATIONS OF ENZYMESELECTIVITY AND STEREOCHEMISTRY

STRUCTURE DETERMINATION OF TETRAHYDROQUINAZOLINEANTIFOALTES IN COMPLEX WITH HUMAN AND PNEUMOCYSTIS CARINIIDIHYDROFOLATE REDUCTASE: CORRELATIONS OF ENZYMESELECTIVITY AND STEREOCHEMISTRY

UNDERSTANDING THE ROLE OF LEU22 VARIANTS IN METHOTREXATERESISTANCE: COMPARISON OF WILD- TYPE AND LEU22ARG VARIANTMOUSE AND HUMAN DIHYDROFOLATE REDUCTASE TERNARY CRYSTALCOMPLEXES WITH METHOTREXATE AND NADPH

UNDERSTANDING THE ROLE OF LEU22 VARIANTS IN METHOTREXATERESISTANCE: COMPARISON OF WILD- TYPE AND LEU22ARG VARIANTMOUSE AND HUMAN DIHYDRFOLATE REDUCTASE TERNARY CRYSTALCOMPLEXES WITH METHOTREXATE AND NADPH

HUMAN DIHYDROFOLATE REDUCTASE COMPLEXED WITH NADPH AND 2,4-DIAMINO-5-((7,8- DICARBAUNDECABORAN-7-YL)METHYL)-6- METHYLPYRIMIDINE, A NOVEL BORON CONTANING, NONCLASSICAL ANTIFOLATE

DIHYDROFOLATE REDUCTASE (DHFR) COMPLEX WITH 5 -DEAZAFOLATE

SHEET
THE SHEET STRUCTURE OF THIS MOLECULE IS BIFURCATED. IN
ORDER TO REPRESENT THIS FEATURE IN THE SHEET RECORDS BELOW,
TWO SHEETS ARE DEFINED.

HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS.

NONCLASSICAL ANTIFOLATES, LIPOPHILIC ANTIFOLATES, NADP, ONE- CARBON METABOLISM, OXIDOREDUCTASE, REDUCTASE