HEADER OXIDO-REDUCTASE 25-JUN-82 3DFR 3DFR 3 COMPND DIHYDROFOLATE REDUCTASE (E.C.1.5.1.3) COMPLEX WITH NADPH AND 3DFR 4 COMPND 2 METHOTREXATE 3DFR 5 SOURCE (LACTOBACILLUS CASEI), DICHLOROMETHOTREXATE-RESISTANT STRAIN 3DFR 6 AUTHOR D.J.FILMAN,D.A.MATTHEWS,J.T.BOLIN,J.KRAUT 3DFR 7 REVDAT 4 31-JAN-84 IDFRC 1 REMARK 3DFRC 1 REVDAT 3 30-SEP-83 3DFRB 1 REVDAT 3DFRB 1 REVDAT 2 07-MAR-83 3DFRA 2 JRNL REMARK CONECT 3DFRB 2 REVDAT 1 21-OCT-82 3DFR 0 3DFRB 3 SPRSDE 21-OCT-82 3DFR 1DFR 3DFRB 4 JRNL AUTH J.T.BOLIN,D.J.FILMAN,D.A.MATTHEWS,R.C.HAMLIN, 3DFR 8 JRNL AUTH 2 J.KRAUT 3DFR 9 JRNL TITL CRYSTAL STRUCTURES OF ESCHERICHIA $COLI AND 3DFRA 1 JRNL TITL 2 LACTOBACILLUS $CASEI DIHYDROFOLATE REDUCTASE 3DFRA 2 JRNL TITL 3 REFINED AT 1.7 ANGSTROMS RESOLUTION. I. GENERAL 3DFRA 3 JRNL TITL 4 FEATURES AND BINDING OF METHOTREXATE 3DFRA 4 JRNL REF J.BIOL.CHEM. V. 257 13650 1982 3DFRA 5 JRNL REFN ASTM JBCHA3 US ISSN 0021-9258 071 3DFRA 6 REMARK 1 3DFR 16 REMARK 1 REFERENCE 1 3DFR 17 REMARK 1 AUTH D.J.FILMAN,J.T.BOLIN,D.A.MATTHEWS,J.KRAUT 3DFR 18 REMARK 1 TITL CRYSTAL STRUCTURES OF ESCHERICHIA $COLI AND 3DFRA 7 REMARK 1 TITL 2 LACTOBACILLUS $CASEI DIHYDROFOLATE REDUCTASE 3DFRA 8 REMARK 1 TITL 3 REFINED AT 1.7 ANGSTROMS RESOLUTION. /II$. 3DFRA 9 REMARK 1 TITL 4 ENVIRONMENT OF BOUND /NADPH$ AND IMPLICATIONS FOR 3DFRA 10 REMARK 1 TITL 5 CATALYSIS 3DFRA 11 REMARK 1 REF J.BIOL.CHEM. V. 257 13663 1982 3DFRA 12 REMARK 1 REFN ASTM JBCHA3 US ISSN 0021-9258 071 3DFRA 13 REMARK 1 REFERENCE 2 3DFR 25 REMARK 1 AUTH K.W.VOLZ,D.A.MATTHEWS,R.A.ALDEN,S.T.FREER,C.HANSCH, 3DFR 26 REMARK 1 AUTH 2 B.T.KAUFMAN,J.KRAUT 3DFR 27 REMARK 1 TITL CRYSTAL STRUCTURE OF AVIAN DIHYDROFOLATE REDUCTASE 3DFR 28 REMARK 1 TITL 2 CONTAINING PHENYLTRIAZINE AND /NADPH$ 3DFR 29 REMARK 1 REF J.BIOL.CHEM. V. 257 2528 1982 3DFR 30 REMARK 1 REFN ASTM JBCHA3 US ISSN 0021-9258 071 3DFR 31 REMARK 1 REFERENCE 3 3DFR 32 REMARK 1 AUTH D.A.MATTHEWS 3DFR 33 REMARK 1 TITL INTERPRETATION OF NUCLEAR MAGNETIC RESONANCE 3DFR 34 REMARK 1 TITL 2 SPECTRA FOR LACTOBACILLUS $CASEI DIHYDROFOLATE 3DFR 35 REMARK 1 TITL 3 REDUCTASE BASED ON THE X-RAY STRUCTURE OF THE 3DFR 36 REMARK 1 TITL 4 ENZYME-*METHOTREXATE-/NADPH$ COMPLEX 3DFR 37 REMARK 1 REF BIOCHEMISTRY V. 18 1602 1979 3DFRC 2 REMARK 1 REFN ASTM BICHAW US ISSN 0006-2960 033 3DFR 39 REMARK 1 REFERENCE 4 3DFR 40 REMARK 1 AUTH D.A.MATTHEWS,R.A.ALDEN,S.T.FREER,N.-H.XUONG,J.KRAUT 3DFR 41 REMARK 1 TITL DIHYDROFOLATE REDUCTASE FROM LACTOBACILLUS $CASEI. 3DFR 42 REMARK 1 TITL 2 STEREOCHEMISTRY OF /NADPH$ BINDING 3DFR 43 REMARK 1 REF J.BIOL.CHEM. V. 254 4144 1979 3DFR 44 REMARK 1 REFN ASTM JBCHA3 US ISSN 0021-9258 071 3DFR 45 REMARK 1 REFERENCE 5 3DFR 46 REMARK 1 AUTH D.A.MATTHEWS,R.A.ALDEN,J.T.BOLIN,D.J.FILMAN, 3DFR 47 REMARK 1 AUTH 2 S.T.FREER,R.HAMLIN,W.G.J.HOL,R.L.KISLIUK, 3DFR 48 REMARK 1 AUTH 3 E.J.PASTORE,L.T.PLANTE,N.-H.XUONG,J.KRAUT 3DFR 49 REMARK 1 TITL DIHYDROFOLATE REDUCTASE FROM LACTOBACILLUS $CASEI. 3DFR 50 REMARK 1 TITL 2 X-RAY STRUCTURE OF THE ENZYME-METHOTREXATE-/NADPH$ 3DFR 51 REMARK 1 TITL 3 COMPLEX 3DFR 52 REMARK 1 REF J.BIOL.CHEM. V. 253 6946 1978 3DFR 53 REMARK 1 REFN ASTM JBCHA3 US ISSN 0021-9258 071 3DFR 54 REMARK 1 REFERENCE 6 3DFR 55 REMARK 1 AUTH D.A.MATTHEWS,R.A.ALDEN,J.T.BOLIN,S.T.FREER, 3DFR 56 REMARK 1 AUTH 2 R.HAMLIN,N.XUONG,J.KRAUT,M.POE,M.WILLIAMS, 3DFR 57 REMARK 1 AUTH 3 K.HOOGSTEEN 3DFR 58 REMARK 1 TITL DIHYDROFOLATE REDUCTASE. X-RAY STRUCTURE OF THE 3DFR 59 REMARK 1 TITL 2 BINARY COMPLEX WITH METHOTREXATE 3DFR 60 REMARK 1 REF SCIENCE V. 197 452 1977 3DFR 61 REMARK 1 REFN ASTM SCIEAS US ISSN 0036-8075 038 3DFR 62 REMARK 1 REFERENCE 7 3DFR 63 REMARK 1 AUTH T.C.CRUSBERG,R.LEARY,R.L.KISLIUK 3DFR 64 REMARK 1 TITL PROPERTIES OF THYMIDYLATE SYNTHETASE FROM 3DFR 65 REMARK 1 TITL 2 DICHLOROMETHOTREXATE-RESISTANT LACTOBACILLUS 3DFR 66 REMARK 1 TITL 3 $CASEI 3DFR 67 REMARK 1 REF J.BIOL.CHEM. V. 245 5292 1970 3DFR 68 REMARK 1 REFN ASTM JBCHA3 US ISSN 0021-9258 071 3DFR 69 REMARK 2 3DFR 70 REMARK 2 RESOLUTION. 1.7 ANGSTROMS 3DFR 71 REMARK 3 3DFR 72 REMARK 3 REFINEMENT. DIFFERENTIAL SYNTHESIS FOLLOWED BY 3DFR 73 REMARK 3 KONNERT-HENDRICKSON LEAST-SQUARES. THE FINAL R VALUE 3DFR 74 REMARK 3 IS 0.152. 3DFR 75 REMARK 4 3DFR 76 REMARK 4 SITE *NDN* COMPRISES THOSE RESIDUES INTERACTING WITH THE 3DFR 77 REMARK 4 ADENINE BASE OF THE NADPH COFACTOR. SITE *NAR* COMPRISES 3DFR 78 REMARK 4 THOSE RESIDUES INTERACTING WITH THE ADENINE MONONUCLEOTIDE 3DFR 79 REMARK 4 RIBOSE OF THE NADPH COFACTOR. SITE *NPP* COMPRISES THOSE 3DFR 80 REMARK 4 RESIDUES INTERACTING WITH PYROPHOSPHATE OF THE NADPH 3DFR 81 REMARK 4 COFACTOR. SITE *NMR* COMPRISES THOSE RESIDUES INTERACTING 3DFR 82 REMARK 4 WITH THE NICOTINAMIDE MONONUCLEOTIDE RIBOSE OF THE NADPH 3DFR 83 REMARK 4 COFACTOR. SITE *NND* COMPRISES THOSE RESIDUES INTERACTING 3DFR 84 REMARK 4 WITH THE NICOTINAMIDE BASE OF THE NADPH COFACTOR. FOR 3DFR 85 REMARK 4 FURTHER DETAILS SEE JRNL REFERENCE ABOVE. 3DFR 86 REMARK 5 3DFR 87 REMARK 5 SITE *MPT* COMPRISES THOSE RESIDUES INTERACTING WITH THE 3DFR 88 REMARK 5 PTERIDINE OF THE METHOTREXATE INHIBITOR. SITE *MNM* 3DFR 89 REMARK 5 COMPRISES TWO RESIDUE INTERACTING WITH THE N(10) METHYL OF 3DFR 90 REMARK 5 THE METHOTREXATE INHIBITOR. SITE *MAB* COMPRISES THOSE 3DFR 91 REMARK 5 RESIDUES INTERACTING WITH THE P-AMINOBENZOYL OF THE 3DFR 92 REMARK 5 METHOTREXATE INHIBITOR. SITE *MGL* COMPRISES THOSE 3DFR 93 REMARK 5 RESIDUES INTERACTING WITH THE GLUTAMATE OF THE METHOTREXATE 3DFR 94 REMARK 5 INHIBITOR. FOR FURTHER DETAILS SEE JRNL REFERENCE ABOVE. 3DFR 95 REMARK 6 3DFR 96 REMARK 6 THE PEPTIDE BONDS LINKING GLY 98 TO GLY 99 AND ARG 52 TO 3DFR 97 REMARK 6 PRO 53 ARE IN THE CIS CONFORMATION. 3DFR 98 REMARK 7 3DFR 99 REMARK 7 THE SIDE CHAIN OF LYS 51 IS MISSING FOUR ATOMS. THESE 3DFR 100 REMARK 7 ATOMS ARE EITHER HIGHLY DISORDERED, OR RESIDUE 51 MAY 3DFR 101 REMARK 7 ACTUALLY BE AN ALANINE IN THIS STRAIN OF L.CASEI. 3DFR 102 REMARK 8 3DFRA 14 REMARK 8 CORRECTION. UPDATE JRNL REFERENCE AND REFERENCE 1 TO 3DFRA 15 REMARK 8 REFLECT PUBLICATION. FIX TYPOGRAPHICAL ERROR ON CONECT 3DFRA 16 REMARK 8 RECORD. 07-MAR-83. 3DFRA 17 REMARK 9 3DFRB 5 REMARK 9 CORRECTION. INSERT REVDAT RECORDS. 30-SEP-83. 3DFRB 6 REMARK 10 3DFRC 3 REMARK 10 CORRECTION. CORRECT JOURNAL NAME FOR REFERENCE 3. 3DFRC 4 REMARK 10 31-JAN-84. 3DFRC 5 SEQRES 1 162 THR ALA PHE LEU TRP ALA GLN ASN ARG ASN GLY LEU ILE 3DFR 103 SEQRES 2 162 GLY LYS ASP GLY HIS LEU PRO TRP HIS LEU PRO ASP ASP 3DFR 104 SEQRES 3 162 LEU HIS TYR PHE ARG ALA GLN THR VAL GLY LYS ILE MET 3DFR 105 SEQRES 4 162 VAL VAL GLY ARG ARG THR TYR GLU SER PHE PRO LYS ARG 3DFR 106 SEQRES 5 162 PRO LEU PRO GLU ARG THR ASN VAL VAL LEU THR HIS GLN 3DFR 107 SEQRES 6 162 GLU ASP TYR GLN ALA GLN GLY ALA VAL VAL VAL HIS ASP 3DFR 108 SEQRES 7 162 VAL ALA ALA VAL PHE ALA TYR ALA LYS GLN HIS LEU ASP 3DFR 109 SEQRES 8 162 GLN GLU LEU VAL ILE ALA GLY GLY ALA GLN ILE PHE THR 3DFR 110 SEQRES 9 162 ALA PHE LYS ASP ASP VAL ASP THR LEU LEU VAL THR ARG 3DFR 111 SEQRES 10 162 LEU ALA GLY SER PHE GLU GLY ASP THR LYS MET ILE PRO 3DFR 112 SEQRES 11 162 LEU ASN TRP ASP ASP PHE THR LYS VAL SER SER ARG THR 3DFR 113 SEQRES 12 162 VAL GLU ASP THR ASN PRO ALA LEU THR HIS THR TYR GLU 3DFR 114 SEQRES 13 162 VAL TRP GLN LYS LYS ALA 3DFR 115 FTNOTE 1 3DFR 116 FTNOTE 1 SEE REMARK 6. 3DFR 117 FTNOTE 2 3DFR 118 FTNOTE 2 SEE REMARK 7. 3DFR 119 HET NDP 1 48 NADPH 3DFR 120 HET MTX 2 33 METHOTREXATE 3DFR 121 FORMUL 2 NDP C21 H27 N7 O17 P3 3DFR 122 FORMUL 3 MTX C20 H22 N8 O5 3DFR 123 FORMUL 4 HOH *264(H2 O1) 3DFR 124 HELIX 1 HB LEU 23 THR 34 1 3DFR 125 HELIX 2 HC GLY 42 PHE 49 1 3DFR 126 HELIX 3 HE ASP 78 HIS 89 1 3DFR 127 HELIX 4 HF GLY 99 LYS 107 1 3DFR 128 SHEET 1 S1 8 VAL 74 VAL 76 0 3DFR 129 SHEET 2 S1 8 GLU 56 THR 63 1 O ASN 59 N VAL 74 3DFR 130 SHEET 3 S1 8 GLY 36 GLY 42 1 O LYS 37 N THR 58 3DFR 131 SHEET 4 S1 8 GLU 93 GLY 98 1 O GLU 93 N ILE 38 3DFR 132 SHEET 5 S1 8 THR 1 GLN 7 1 N ALA 2 O LEU 94 3DFR 133 SHEET 6 S1 8 ASP 111 ALA 119 1 O THR 112 N PHE 3 3DFR 134 SHEET 7 S1 8 THR 152 LYS 161 -1 N LYS 160 O ASP 111 3DFR 135 SHEET 8 S1 8 ASP 135 VAL 144 -1 N THR 137 O GLN 159 3DFR 136 TURN 1 TA ASN 8 GLY 11 3DFR 137 TURN 2 TB LYS 15 HIS 18 3DFR 138 TURN 3 TC THR 34 LYS 37 3DFR 139 TURN 4 TD LYS 51 LEU 54 NOT FOUND IN E.COLI DHFR 3DFR 140 TURN 5 TE LEU 54 ARG 57 3DFR 141 TURN 6 TF GLN 65 TYR 68 NOT FOUND IN E.COLI DHFR 3DFR 142 TURN 7 TG ALA 70 ALA 73 3DFR 143 TURN 8 TH HIS 89 GLN 92 3DFR 144 TURN 9 TI PHE 106 ASP 109 LINKED WITH TURN TJ 3DFR 145 TURN 10 TJ LYS 107 VAL 110 LINKED WITH TURN TI 3DFR 146 TURN 11 TK ASN 132 ASP 135 LINKED WITH TURN TL 3DFR 147 TURN 12 TL TRP 133 PHE 136 LINKED WITH TURN TK 3DFR 148 TURN 13 TM ASP 146 PRO 149 LINKED WITH TURNS TN, TO 3DFR 149 TURN 14 TN ASN 148 LEU 151 LINKED WITH TURNS TM, TO 3DFR 150 TURN 15 TO PRO 149 THR 152 LINKED WITH TURNS TM, TN 3DFR 151 SITE 1 NDN 8 LEU 62 THR 63 HIS 64 HIS 77 3DFR 152 SITE 2 NDN 8 GLN 101 ILE 102 HOH 279 HOH 318 3DFR 153 SITE 1 NAR 9 GLY 42 ARG 43 ARG 44 THR 63 3DFR 154 SITE 2 NAR 9 HIS 64 GLN 65 GLN 101 ILE 102 3DFR 155 SITE 3 NAR 9 HOH 401 3DFR 156 SITE 1 NPP 7 ARG 44 THR 45 GLY 99 GLN 101 3DFR 157 SITE 2 NPP 7 ILE 102 THR 126 HOH 301 3DFR 158 SITE 1 NMR 7 ILE 13 GLY 14 HIS 18 SER 48 3DFR 159 SITE 2 NMR 7 GLY 99 HOH 208 HOH 439 3DFR 160 SITE 1 NND 12 TRP 5 ALA 6 ILE 13 LEU 19 3DFR 161 SITE 2 NND 12 TRP 21 THR 45 ALA 97 GLY 98 3DFR 162 SITE 3 NND 12 GLY 99 PHE 103 MTX 2 HOH 439 3DFR 163 SITE 1 MPT 14 LEU 4 TRP 5 ALA 6 LEU 19 3DFR 164 SITE 2 MPT 14 TRP 21 ASP 26 LEU 27 PHE 30 3DFR 165 SITE 3 MPT 14 ALA 97 THR 116 NDP 1 HOH 201 3DFR 166 SITE 4 MPT 14 HOH 217 HOH 253 3DFR 167 SITE 1 MNM 2 LEU 19 SER 48 3DFR 168 SITE 1 MAB 5 LEU 27 PHE 30 PHE 49 PRO 50 3DFR 169 SITE 2 MAB 5 LEU 54 3DFR 170 SITE 1 MGL 6 LEU 27 HIS 28 PHE 30 ARG 31 3DFR 171 SITE 2 MGL 6 LEU 54 ARG 57 3DFR 172 CRYST1 71.860 71.860 93.380 90.00 90.00 120.00 P 61 6 3DFR 173 ORIGX1 .013916 .008034 0.000000 0.00000 3DFR 174 ORIGX2 0.000000 .016069 0.000000 0.00000 3DFR 175 ORIGX3 0.000000 0.000000 .010709 0.00000 3DFR 176 SCALE1 .013916 .008034 0.000000 0.00000 3DFR 177 SCALE2 0.000000 .016069 0.000000 0.00000 3DFR 178 SCALE3 0.000000 0.000000 .010709 0.00000 3DFR 179