HEADER LIPOPROTEIN 22-AUG-91 1LPE 1LPE 2 COMPND APOLIPOPROTEIN-*E3 (/LDL$ RECEPTOR BINDING DOMAIN) 1LPE 3 SOURCE HUMAN (HOMO $SAPIENS) 1LPE 4 AUTHOR C.WILSON,D.A.AGARD 1LPE 5 REVDAT 1 15-OCT-92 1LPE 0 1LPE 6 JRNL AUTH C.WILSON,M.R.WARDELL,K.H.WEISGRABER,R.W.MAHLEY, 1LPE 7 JRNL AUTH 2 D.A.AGARD 1LPE 8 JRNL TITL THREE-*DIMENSIONAL STRUCTURE OF THE /LDL$ 1LPE 9 JRNL TITL 2 RECEPTOR-*BINDING DOMAIN OF HUMAN APOLIPOPROTEIN E 1LPE 10 JRNL REF SCIENCE V. 252 1817 1991 1LPE 11 JRNL REFN ASTM SCIEAS US ISSN 0036-8075 038 1LPE 12 REMARK 1 1LPE 13 REMARK 1 REFERENCE 1 1LPE 14 REMARK 1 AUTH L.P.AGGERBECK,J.R.WETTERAU,K.H.WEISGRABER, 1LPE 15 REMARK 1 AUTH 2 R.W.MAHLEY,D.A.AGARD 1LPE 16 REMARK 1 TITL CRYSTALLIZATION AND PRELIMINARY X-RAY DIFFRACTION 1LPE 17 REMARK 1 TITL 2 STUDIES ON THE AMINO-TERMINAL (RECEPTOR-BINDING) 1LPE 18 REMARK 1 TITL 3 DOMAIN OF HUMAN APOLIPOPROTEIN E3 FROM SERUM 1LPE 19 REMARK 1 TITL 4 VERY LOW DENSITY LIPOPROTEINS 1LPE 20 REMARK 1 REF J.MOL.BIOL. V. 202 179 1988 1LPE 21 REMARK 1 REFN ASTM JMOBAK UK ISSN 0022-2836 070 1LPE 22 REMARK 2 1LPE 23 REMARK 2 RESOLUTION. 2.25 ANGSTROMS. 1LPE 24 REMARK 3 1LPE 25 REMARK 3 REFINEMENT. MOLECULAR DYNAMICS REFINEMENT BY THE METHOD OF 1LPE 26 REMARK 3 A. BRUNGER, J. KURIYAN, AND M. KARPLUS (PROGRAM *XPLOR*). 1LPE 27 REMARK 3 THE R VALUE IS 0.175. THE RMS DEVIATION FROM IDEALITY OF 1LPE 28 REMARK 3 THE BOND LENGTHS IS 0.017 ANGSTROMS. THE RMS DEVIATION 1LPE 29 REMARK 3 FROM IDEALITY OF THE BOND ANGLES IS 3.2 DEGREES. 1LPE 30 REMARK 4 1LPE 31 REMARK 4 APOLIPOPROTEIN E CONTAINS TWO STABLE DOMAINS WHICH CAN BE 1LPE 32 REMARK 4 MODELED BY 22-KD AND 10-KD THROMBOLYTIC FRAGMENTS. THE 1LPE 33 REMARK 4 22-KD AMINO-TERMINAL DOMAIN (191 AMINO ACIDS) IS 1LPE 34 REMARK 4 RESPONSIBLE FOR THE HIGH AFFINITY BINDING OF APO-E TO THE 1LPE 35 REMARK 4 LOW DENSITY LIPOPROTEIN (LDL) RECEPTOR. RESIDUES 1 TO 22 1LPE 36 REMARK 4 AND 167 TO 191 APPEAR TO BE DISORDERED IN THE CRYSTAL AND 1LPE 37 REMARK 4 ARE MISSING FROM THE REFINED MODEL. RESIDUE NUMBERING 1LPE 38 REMARK 4 CORRESPONDS TO THE AMINO ACID SEQUENCE FOR THE INTACT 1LPE 39 REMARK 4 PROTEIN. THE FINAL STRUCTURE ALSO CONTAINS 121 WATER 1LPE 40 REMARK 4 MOLECULES, NUMBERED SEQUENTIALLY STARTING AT 192. 1LPE 41 REMARK 5 1LPE 42 REMARK 5 THREE ISOFORMS OF APO-E ARE RELATIVELY COMMON. THE 1LPE 43 REMARK 5 STRUCTURE WAS SOLVED USING THE MOST FREQUENTLY OCCURRING 1LPE 44 REMARK 5 ISOFORM, APO-E3. 1LPE 45 REMARK 6 1LPE 46 REMARK 6 X-RAY DATA WAS COLLECTED AT -150OC TO MINIMIZE RADIATION 1LPE 47 REMARK 6 DECAY. PHASE INFORMATION WAS PROVIDED BY ISOMORPHOUS AND 1LPE 48 REMARK 6 ANOMALOUS DIFFERENCES MEASURED FOR THE DIMETHYL MERCURY 1LPE 49 REMARK 6 DERIVATIVE. EXTENSIVE SOLVENT FLATTENING (B.C. WANG 1LPE 50 REMARK 6 PROGRAMS) WAS USED TO REFINE THE PHASES PRIOR TO BUILDING 1LPE 51 REMARK 6 AN ATOMIC MODEL. 1LPE 52 REMARK 7 1LPE 53 REMARK 7 THE LOOP CONNECTING THE SECOND AND THIRD HELICES OF THE 1LPE 54 REMARK 7 FOUR-HELIX BUNDLE (RESIDUES 83-88) IS POORLY DEFINED IN 1LPE 55 REMARK 7 THE ELECTRON DENSITY MAP. X-PLOR-REFINED COORDINATES FOR 1LPE 56 REMARK 7 THE LOOP HAVE BEEN INCLUDED IN THE STRUCTURE BUT ARE LIKELY 1LPE 57 REMARK 7 TO CONTAIN ERRORS. 1LPE 58 REMARK 8 1LPE 59 REMARK 8 SECONDARY STRUCTURE WAS ASSIGNED USING THE *DEFINE* PROGRAM 1LPE 60 REMARK 8 (RICHARDS AND KUNDROT, PROTEINS V. 3, 71 (1988)). 1LPE 61 SEQRES 1 144 GLY GLN ARG TRP GLU LEU ALA LEU GLY ARG PHE TRP ASP 1LPE 62 SEQRES 2 144 TYR LEU ARG TRP VAL GLN THR LEU SER GLU GLN VAL GLN 1LPE 63 SEQRES 3 144 GLU GLU LEU LEU SER SER GLN VAL THR GLN GLU LEU ARG 1LPE 64 SEQRES 4 144 ALA LEU MET ASP GLU THR MET LYS GLU LEU LYS ALA TYR 1LPE 65 SEQRES 5 144 LYS SER GLU LEU GLU GLU GLN LEU THR PRO VAL ALA GLU 1LPE 66 SEQRES 6 144 GLU THR ARG ALA ARG LEU SER LYS GLU LEU GLN ALA ALA 1LPE 67 SEQRES 7 144 GLN ALA ARG LEU GLY ALA ASP MET GLU ASP VAL CYS GLY 1LPE 68 SEQRES 8 144 ARG LEU VAL GLN TYR ARG GLY GLU VAL GLN ALA MET LEU 1LPE 69 SEQRES 9 144 GLY GLN SER THR GLU GLU LEU ARG VAL ARG LEU ALA SER 1LPE 70 SEQRES 10 144 HIS LEU ARG LYS LEU ARG LYS ARG LEU LEU ARG ASP ALA 1LPE 71 SEQRES 11 144 ASP ASP LEU GLN LYS ARG LEU ALA VAL TYR GLN ALA GLY 1LPE 72 SEQRES 12 144 ALA 1LPE 73 FORMUL 2 HOH *121(H2 O1) 1LPE 74 HELIX 1 H1 GLN 24 THR 42 1 1LPE 75 HELIX 2 HC SER 44 SER 53 1 1LPE 76 HELIX 3 H2 SER 54 GLN 81 1 1LPE 77 HELIX 4 H3 GLU 87 VAL 122 1 1LPE 78 HELIX 5 H4 THR 130 ALA 164 1 1LPE 79 CRYST1 40.650 53.960 85.430 90.00 90.00 90.00 P 21 21 21 4 1LPE 80 ORIGX1 1.000000 0.000000 0.000000 0.00000 1LPE 81 ORIGX2 0.000000 1.000000 0.000000 0.00000 1LPE 82 ORIGX3 0.000000 0.000000 1.000000 0.00000 1LPE 83 SCALE1 0.024600 0.000000 0.000000 0.00000 1LPE 84 SCALE2 0.000000 0.018532 0.000000 0.00000 1LPE 85 SCALE3 0.000000 0.000000 0.011705 0.00000 1LPE 86