HEADER SIGNALING PROTEIN/IMMUNE SYSTEM 02-DEC-24 9KT7 TITLE CRYO-EM STRUCTURE OF HCA2-GI COMPLEX WITH MK6892 COMPND MOL_ID: 1; COMPND 2 MOLECULE: HYDROXYCARBOXYLIC ACID RECEPTOR 2; COMPND 3 CHAIN: R; COMPND 4 SYNONYM: G-PROTEIN COUPLED RECEPTOR 109A,G-PROTEIN COUPLED RECEPTOR COMPND 5 HM74A,NIACIN RECEPTOR 1,NICOTINIC ACID RECEPTOR; COMPND 6 ENGINEERED: YES; COMPND 7 MOL_ID: 2; COMPND 8 MOLECULE: GUANINE NUCLEOTIDE-BINDING PROTEIN G(I) SUBUNIT ALPHA-1; COMPND 9 CHAIN: A; COMPND 10 SYNONYM: ADENYLATE CYCLASE-INHIBITING G ALPHA PROTEIN; COMPND 11 ENGINEERED: YES; COMPND 12 MOL_ID: 3; COMPND 13 MOLECULE: GUANINE NUCLEOTIDE-BINDING PROTEIN G(I)/G(S)/G(T) SUBUNIT COMPND 14 BETA-1; COMPND 15 CHAIN: B; COMPND 16 SYNONYM: TRANSDUCIN BETA CHAIN 1; COMPND 17 ENGINEERED: YES; COMPND 18 MOL_ID: 4; COMPND 19 MOLECULE: GUANINE NUCLEOTIDE-BINDING PROTEIN G(I)/G(S)/G(O) SUBUNIT COMPND 20 GAMMA-2; COMPND 21 CHAIN: C; COMPND 22 SYNONYM: G GAMMA-I; COMPND 23 ENGINEERED: YES; COMPND 24 MOL_ID: 5; COMPND 25 MOLECULE: SCFV; COMPND 26 CHAIN: E; COMPND 27 ENGINEERED: YES SOURCE MOL_ID: 1; SOURCE 2 ORGANISM_SCIENTIFIC: HOMO SAPIENS; SOURCE 3 ORGANISM_COMMON: HUMAN; SOURCE 4 ORGANISM_TAXID: 9606; SOURCE 5 GENE: HCAR2, GPR109A, HCA2, HM74A, NIACR1; SOURCE 6 EXPRESSION_SYSTEM: SPODOPTERA FRUGIPERDA; SOURCE 7 EXPRESSION_SYSTEM_TAXID: 7108; SOURCE 8 MOL_ID: 2; SOURCE 9 ORGANISM_SCIENTIFIC: HOMO SAPIENS; SOURCE 10 ORGANISM_COMMON: HUMAN; SOURCE 11 ORGANISM_TAXID: 9606; SOURCE 12 GENE: GNAI1; SOURCE 13 EXPRESSION_SYSTEM: SPODOPTERA FRUGIPERDA; SOURCE 14 EXPRESSION_SYSTEM_TAXID: 7108; SOURCE 15 MOL_ID: 3; SOURCE 16 ORGANISM_SCIENTIFIC: HOMO SAPIENS; SOURCE 17 ORGANISM_COMMON: HUMAN; SOURCE 18 ORGANISM_TAXID: 9606; SOURCE 19 GENE: GNB1; SOURCE 20 EXPRESSION_SYSTEM: SPODOPTERA FRUGIPERDA; SOURCE 21 EXPRESSION_SYSTEM_TAXID: 7108; SOURCE 22 MOL_ID: 4; SOURCE 23 ORGANISM_SCIENTIFIC: HOMO SAPIENS; SOURCE 24 ORGANISM_COMMON: HUMAN; SOURCE 25 ORGANISM_TAXID: 9606; SOURCE 26 GENE: GNG2; SOURCE 27 EXPRESSION_SYSTEM: SPODOPTERA FRUGIPERDA; SOURCE 28 EXPRESSION_SYSTEM_TAXID: 7108; SOURCE 29 MOL_ID: 5; SOURCE 30 ORGANISM_SCIENTIFIC: HOMO SAPIENS; SOURCE 31 ORGANISM_TAXID: 9606; SOURCE 32 EXPRESSION_SYSTEM: SPODOPTERA FRUGIPERDA; SOURCE 33 EXPRESSION_SYSTEM_TAXID: 7108 KEYWDS CRYO-EM; G-PROTEIN-COUPLED RECEPTORS; HYDROXYCARBOXYLIC ACID KEYWDS 2 RECEPTORS, SIGNALING PROTEIN/IMMUNE SYSTEM, SIGNALING PROTEIN-IMMUNE KEYWDS 3 SYSTEM COMPLEX EXPDTA ELECTRON MICROSCOPY AUTHOR S.WU,S.WU REVDAT 1 10-DEC-25 9KT7 0 JRNL AUTH J.WANG,Y.QIAN,Z.HAN,Y.WANG,Y.LIU,J.LI,Q.DUANMU,S.YE,A.QIAO, JRNL AUTH 2 S.WU JRNL TITL INSIGHTS INTO THE ACTIVATION MECHANISM OF HCA1, HCA2, AND JRNL TITL 2 HCA3. JRNL REF J.MED.CHEM. V. 68 4527 2025 JRNL REFN ISSN 0022-2623 JRNL PMID 39936872 JRNL DOI 10.1021/ACS.JMEDCHEM.4C02567 REMARK 2 REMARK 2 RESOLUTION. 2.80 ANGSTROMS. REMARK 3 REMARK 3 REFINEMENT. REMARK 3 SOFTWARE PACKAGES : PHENIX REMARK 3 RECONSTRUCTION SCHEMA : NULL REMARK 3 REMARK 3 EM MAP-MODEL FITTING AND REFINEMENT REMARK 3 PDB ENTRY : NULL REMARK 3 REFINEMENT SPACE : NULL REMARK 3 REFINEMENT PROTOCOL : NULL REMARK 3 REFINEMENT TARGET : NULL REMARK 3 OVERALL ANISOTROPIC B VALUE : NULL REMARK 3 REMARK 3 FITTING PROCEDURE : NULL REMARK 3 REMARK 3 EM IMAGE RECONSTRUCTION STATISTICS REMARK 3 NOMINAL PIXEL SIZE (ANGSTROMS) : NULL REMARK 3 ACTUAL PIXEL SIZE (ANGSTROMS) : NULL REMARK 3 EFFECTIVE RESOLUTION (ANGSTROMS) : 2.800 REMARK 3 NUMBER OF PARTICLES : 874405 REMARK 3 CTF CORRECTION METHOD : PHASE FLIPPING AND AMPLITUDE REMARK 3 CORRECTION REMARK 3 REMARK 3 EM RECONSTRUCTION MAGNIFICATION CALIBRATION: NULL REMARK 3 REMARK 3 OTHER DETAILS: NULL REMARK 4 REMARK 4 9KT7 COMPLIES WITH FORMAT V. 3.30, 13-JUL-11 REMARK 100 REMARK 100 THIS ENTRY HAS BEEN PROCESSED BY PDBC ON 04-DEC-24. REMARK 100 THE DEPOSITION ID IS D_1300051097. REMARK 245 REMARK 245 EXPERIMENTAL DETAILS REMARK 245 RECONSTRUCTION METHOD : SINGLE PARTICLE REMARK 245 SPECIMEN TYPE : NULL REMARK 245 REMARK 245 ELECTRON MICROSCOPE SAMPLE REMARK 245 SAMPLE TYPE : PARTICLE REMARK 245 PARTICLE TYPE : POINT REMARK 245 NAME OF SAMPLE : HCA2-GI COMPLEX WITH MK6892 REMARK 245 SAMPLE CONCENTRATION (MG ML-1) : NULL REMARK 245 SAMPLE SUPPORT DETAILS : NULL REMARK 245 SAMPLE VITRIFICATION DETAILS : NULL REMARK 245 SAMPLE BUFFER : NULL REMARK 245 PH : 7.50 REMARK 245 SAMPLE DETAILS : NULL REMARK 245 REMARK 245 DATA ACQUISITION REMARK 245 DATE OF EXPERIMENT : NULL REMARK 245 NUMBER OF MICROGRAPHS-IMAGES : NULL REMARK 245 TEMPERATURE (KELVIN) : NULL REMARK 245 MICROSCOPE MODEL : FEI TITAN KRIOS REMARK 245 DETECTOR TYPE : GATAN K3 BIOQUANTUM (6K X REMARK 245 4K) REMARK 245 MINIMUM DEFOCUS (NM) : 1000.00 REMARK 245 MAXIMUM DEFOCUS (NM) : 1500.00 REMARK 245 MINIMUM TILT ANGLE (DEGREES) : NULL REMARK 245 MAXIMUM TILT ANGLE (DEGREES) : NULL REMARK 245 NOMINAL CS : NULL REMARK 245 IMAGING MODE : BRIGHT FIELD REMARK 245 ELECTRON DOSE (ELECTRONS NM**-2) : 5400.00 REMARK 245 ILLUMINATION MODE : FLOOD BEAM REMARK 245 NOMINAL MAGNIFICATION : NULL REMARK 245 CALIBRATED MAGNIFICATION : NULL REMARK 245 SOURCE : FIELD EMISSION GUN REMARK 245 ACCELERATION VOLTAGE (KV) : 300 REMARK 245 IMAGING DETAILS : NULL REMARK 247 REMARK 247 ELECTRON MICROSCOPY REMARK 247 THE COORDINATES IN THIS ENTRY WERE GENERATED FROM ELECTRON REMARK 247 MICROSCOPY DATA. PROTEIN DATA BANK CONVENTIONS REQUIRE REMARK 247 THAT CRYST1 AND SCALE RECORDS BE INCLUDED, BUT THE VALUES REMARK 247 ON THESE RECORDS ARE MEANINGLESS EXCEPT FOR THE CALCULATION REMARK 247 OF THE STRUCTURE FACTORS. REMARK 300 REMARK 300 BIOMOLECULE: 1 REMARK 300 SEE REMARK 350 FOR THE AUTHOR PROVIDED AND/OR PROGRAM REMARK 300 GENERATED ASSEMBLY INFORMATION FOR THE STRUCTURE IN REMARK 300 THIS ENTRY. THE REMARK MAY ALSO PROVIDE INFORMATION ON REMARK 300 BURIED SURFACE AREA. REMARK 350 REMARK 350 COORDINATES FOR A COMPLETE MULTIMER REPRESENTING THE KNOWN REMARK 350 BIOLOGICALLY SIGNIFICANT OLIGOMERIZATION STATE OF THE REMARK 350 MOLECULE CAN BE GENERATED BY APPLYING BIOMT TRANSFORMATIONS REMARK 350 GIVEN BELOW. BOTH NON-CRYSTALLOGRAPHIC AND REMARK 350 CRYSTALLOGRAPHIC OPERATIONS ARE GIVEN. REMARK 350 REMARK 350 BIOMOLECULE: 1 REMARK 350 AUTHOR DETERMINED BIOLOGICAL UNIT: PENTAMERIC REMARK 350 APPLY THE FOLLOWING TO CHAINS: R, A, B, C, E REMARK 350 BIOMT1 1 1.000000 0.000000 0.000000 0.00000 REMARK 350 BIOMT2 1 0.000000 1.000000 0.000000 0.00000 REMARK 350 BIOMT3 1 0.000000 0.000000 1.000000 0.00000 REMARK 465 REMARK 465 MISSING RESIDUES REMARK 465 THE FOLLOWING RESIDUES WERE NOT LOCATED IN THE REMARK 465 EXPERIMENT. (M=MODEL NUMBER; RES=RESIDUE NAME; C=CHAIN REMARK 465 IDENTIFIER; SSSEQ=SEQUENCE NUMBER; I=INSERTION CODE.) REMARK 465 REMARK 465 M RES C SSSEQI REMARK 465 MET R 1 REMARK 465 ASN R 2 REMARK 465 ARG R 3 REMARK 465 HIS R 4 REMARK 465 HIS R 5 REMARK 465 LEU R 6 REMARK 465 GLN R 7 REMARK 465 ASP R 8 REMARK 465 PHE R 301 REMARK 465 PRO R 302 REMARK 465 ASN R 303 REMARK 465 PHE R 304 REMARK 465 PHE R 305 REMARK 465 SER R 306 REMARK 465 THR R 307 REMARK 465 LEU R 308 REMARK 465 ILE R 309 REMARK 465 ASN R 310 REMARK 465 ARG R 311 REMARK 465 CYS R 312 REMARK 465 LEU R 313 REMARK 465 GLN R 314 REMARK 465 ARG R 315 REMARK 465 LYS R 316 REMARK 465 MET R 317 REMARK 465 THR R 318 REMARK 465 GLY R 319 REMARK 465 GLU R 320 REMARK 465 PRO R 321 REMARK 465 ASP R 322 REMARK 465 ASN R 323 REMARK 465 ASN R 324 REMARK 465 ARG R 325 REMARK 465 SER R 326 REMARK 465 THR R 327 REMARK 465 SER R 328 REMARK 465 VAL R 329 REMARK 465 GLU R 330 REMARK 465 LEU R 331 REMARK 465 THR R 332 REMARK 465 GLY R 333 REMARK 465 ASP R 334 REMARK 465 PRO R 335 REMARK 465 ASN R 336 REMARK 465 LYS R 337 REMARK 465 THR R 338 REMARK 465 ARG R 339 REMARK 465 GLY R 340 REMARK 465 ALA R 341 REMARK 465 PRO R 342 REMARK 465 GLU R 343 REMARK 465 ALA R 344 REMARK 465 LEU R 345 REMARK 465 MET R 346 REMARK 465 ALA R 347 REMARK 465 ASN R 348 REMARK 465 SER R 349 REMARK 465 GLY R 350 REMARK 465 GLU R 351 REMARK 465 PRO R 352 REMARK 465 TRP R 353 REMARK 465 SER R 354 REMARK 465 PRO R 355 REMARK 465 SER R 356 REMARK 465 TYR R 357 REMARK 465 LEU R 358 REMARK 465 GLY R 359 REMARK 465 PRO R 360 REMARK 465 THR R 361 REMARK 465 SER R 362 REMARK 465 PRO R 363 REMARK 465 MET A 1 REMARK 465 ILE A 56 REMARK 465 HIS A 57 REMARK 465 GLU A 58 REMARK 465 ALA A 59 REMARK 465 GLY A 60 REMARK 465 TYR A 61 REMARK 465 SER A 62 REMARK 465 GLU A 63 REMARK 465 GLU A 64 REMARK 465 GLU A 65 REMARK 465 CYS A 66 REMARK 465 LYS A 67 REMARK 465 GLN A 68 REMARK 465 TYR A 69 REMARK 465 LYS A 70 REMARK 465 ALA A 71 REMARK 465 VAL A 72 REMARK 465 VAL A 73 REMARK 465 TYR A 74 REMARK 465 SER A 75 REMARK 465 ASN A 76 REMARK 465 THR A 77 REMARK 465 ILE A 78 REMARK 465 GLN A 79 REMARK 465 SER A 80 REMARK 465 ILE A 81 REMARK 465 ILE A 82 REMARK 465 ALA A 83 REMARK 465 ILE A 84 REMARK 465 ILE A 85 REMARK 465 ARG A 86 REMARK 465 ALA A 87 REMARK 465 MET A 88 REMARK 465 GLY A 89 REMARK 465 ARG A 90 REMARK 465 LEU A 91 REMARK 465 LYS A 92 REMARK 465 ILE A 93 REMARK 465 ASP A 94 REMARK 465 PHE A 95 REMARK 465 GLY A 96 REMARK 465 ASP A 97 REMARK 465 SER A 98 REMARK 465 ALA A 99 REMARK 465 ARG A 100 REMARK 465 ALA A 101 REMARK 465 ASP A 102 REMARK 465 ASP A 103 REMARK 465 ALA A 104 REMARK 465 ARG A 105 REMARK 465 GLN A 106 REMARK 465 LEU A 107 REMARK 465 PHE A 108 REMARK 465 VAL A 109 REMARK 465 LEU A 110 REMARK 465 ALA A 111 REMARK 465 GLY A 112 REMARK 465 ALA A 113 REMARK 465 ALA A 114 REMARK 465 GLU A 115 REMARK 465 GLU A 116 REMARK 465 GLY A 117 REMARK 465 PHE A 118 REMARK 465 MET A 119 REMARK 465 THR A 120 REMARK 465 ALA A 121 REMARK 465 GLU A 122 REMARK 465 LEU A 123 REMARK 465 ALA A 124 REMARK 465 GLY A 125 REMARK 465 VAL A 126 REMARK 465 ILE A 127 REMARK 465 LYS A 128 REMARK 465 ARG A 129 REMARK 465 LEU A 130 REMARK 465 TRP A 131 REMARK 465 LYS A 132 REMARK 465 ASP A 133 REMARK 465 SER A 134 REMARK 465 GLY A 135 REMARK 465 VAL A 136 REMARK 465 GLN A 137 REMARK 465 ALA A 138 REMARK 465 CYS A 139 REMARK 465 PHE A 140 REMARK 465 ASN A 141 REMARK 465 ARG A 142 REMARK 465 SER A 143 REMARK 465 ARG A 144 REMARK 465 GLU A 145 REMARK 465 TYR A 146 REMARK 465 GLN A 147 REMARK 465 LEU A 148 REMARK 465 ASN A 149 REMARK 465 ASP A 150 REMARK 465 SER A 151 REMARK 465 ALA A 152 REMARK 465 ALA A 153 REMARK 465 TYR A 154 REMARK 465 TYR A 155 REMARK 465 LEU A 156 REMARK 465 ASN A 157 REMARK 465 ASP A 158 REMARK 465 LEU A 159 REMARK 465 ASP A 160 REMARK 465 ARG A 161 REMARK 465 ILE A 162 REMARK 465 ALA A 163 REMARK 465 GLN A 164 REMARK 465 PRO A 165 REMARK 465 ASN A 166 REMARK 465 TYR A 167 REMARK 465 ILE A 168 REMARK 465 PRO A 169 REMARK 465 THR A 170 REMARK 465 GLN A 171 REMARK 465 GLN A 172 REMARK 465 ASP A 173 REMARK 465 VAL A 174 REMARK 465 LEU A 175 REMARK 465 ARG A 176 REMARK 465 THR A 177 REMARK 465 ARG A 178 REMARK 465 VAL A 179 REMARK 465 LYS A 180 REMARK 465 MET C 1 REMARK 465 ALA C 2 REMARK 465 SER C 3 REMARK 465 ASN C 4 REMARK 465 ASN C 5 REMARK 465 GLU C 63 REMARK 465 LYS C 64 REMARK 465 LYS C 65 REMARK 465 PHE C 66 REMARK 465 PHE C 67 REMARK 465 CYS C 68 REMARK 465 ALA C 69 REMARK 465 ILE C 70 REMARK 465 LEU C 71 REMARK 465 GLY E 122 REMARK 465 GLY E 123 REMARK 465 GLY E 124 REMARK 465 GLY E 125 REMARK 465 SER E 126 REMARK 465 GLY E 127 REMARK 465 GLY E 128 REMARK 465 GLY E 129 REMARK 465 GLY E 130 REMARK 465 SER E 131 REMARK 465 GLY E 132 REMARK 465 GLY E 133 REMARK 465 GLY E 134 REMARK 465 GLY E 135 REMARK 465 LYS E 248 REMARK 465 ALA E 249 REMARK 465 ALA E 250 REMARK 465 ALA E 251 REMARK 465 LEU E 252 REMARK 465 GLU E 253 REMARK 465 VAL E 254 REMARK 465 LEU E 255 REMARK 465 PHE E 256 REMARK 465 GLN E 257 REMARK 465 GLY E 258 REMARK 465 PRO E 259 REMARK 465 HIS E 260 REMARK 465 HIS E 261 REMARK 465 HIS E 262 REMARK 465 HIS E 263 REMARK 465 HIS E 264 REMARK 465 HIS E 265 REMARK 465 HIS E 266 REMARK 465 HIS E 267 REMARK 500 REMARK 500 GEOMETRY AND STEREOCHEMISTRY REMARK 500 SUBTOPIC: CLOSE CONTACTS IN SAME ASYMMETRIC UNIT REMARK 500 REMARK 500 THE FOLLOWING ATOMS ARE IN CLOSE CONTACT. REMARK 500 REMARK 500 ATM1 RES C SSEQI ATM2 RES C SSEQI DISTANCE REMARK 500 OH TYR A 290 OE1 GLU A 298 2.09 REMARK 500 REMARK 500 REMARK: NULL REMARK 500 REMARK 500 GEOMETRY AND STEREOCHEMISTRY REMARK 500 SUBTOPIC: TORSION ANGLES REMARK 500 REMARK 500 TORSION ANGLES OUTSIDE THE EXPECTED RAMACHANDRAN REGIONS: REMARK 500 (M=MODEL NUMBER; RES=RESIDUE NAME; C=CHAIN IDENTIFIER; REMARK 500 SSEQ=SEQUENCE NUMBER; I=INSERTION CODE). REMARK 500 REMARK 500 STANDARD TABLE: REMARK 500 FORMAT:(10X,I3,1X,A3,1X,A1,I4,A1,4X,F7.2,3X,F7.2) REMARK 500 REMARK 500 EXPECTED VALUES: GJ KLEYWEGT AND TA JONES (1996). PHI/PSI- REMARK 500 CHOLOGY: RAMACHANDRAN REVISITED. STRUCTURE 4, 1395 - 1400 REMARK 500 REMARK 500 M RES CSSEQI PSI PHI REMARK 500 ASP R 14 -166.60 -119.02 REMARK 500 HIS R 131 78.49 -114.89 REMARK 500 HIS R 133 73.21 -100.09 REMARK 500 MET R 167 172.62 65.42 REMARK 500 LYS A 314 -2.05 65.16 REMARK 500 THR A 329 -2.75 66.48 REMARK 500 ARG B 137 143.33 -171.15 REMARK 500 PHE B 292 1.87 80.64 REMARK 500 ASP C 48 88.52 -158.01 REMARK 500 VAL E 48 -56.70 -124.81 REMARK 500 MET E 192 -13.38 74.28 REMARK 500 REMARK 500 REMARK: NULL REMARK 900 REMARK 900 RELATED ENTRIES REMARK 900 RELATED ID: EMD-62558 RELATED DB: EMDB REMARK 900 CRYO-EM STRUCTURE OF HCA2-GI COMPLEX WITH MK6892 DBREF 9KT7 R 1 363 UNP Q8TDS4 HCAR2_HUMAN 1 363 DBREF 9KT7 A 1 354 UNP P63096 GNAI1_HUMAN 1 354 DBREF 9KT7 B 2 340 UNP P62873 GBB1_HUMAN 2 340 DBREF 9KT7 C 1 71 UNP P59768 GBG2_HUMAN 1 71 DBREF 9KT7 E 1 267 PDB 9KT7 9KT7 1 267 SEQADV 9KT7 ASN A 47 UNP P63096 SER 47 ENGINEERED MUTATION SEQADV 9KT7 ALA A 203 UNP P63096 GLY 203 ENGINEERED MUTATION SEQADV 9KT7 ALA A 245 UNP P63096 GLU 245 ENGINEERED MUTATION SEQADV 9KT7 SER A 326 UNP P63096 ALA 326 ENGINEERED MUTATION SEQADV 9KT7 GLN B 1 UNP P62873 EXPRESSION TAG SEQRES 1 R 363 MET ASN ARG HIS HIS LEU GLN ASP HIS PHE LEU GLU ILE SEQRES 2 R 363 ASP LYS LYS ASN CYS CYS VAL PHE ARG ASP ASP PHE ILE SEQRES 3 R 363 VAL LYS VAL LEU PRO PRO VAL LEU GLY LEU GLU PHE ILE SEQRES 4 R 363 PHE GLY LEU LEU GLY ASN GLY LEU ALA LEU TRP ILE PHE SEQRES 5 R 363 CYS PHE HIS LEU LYS SER TRP LYS SER SER ARG ILE PHE SEQRES 6 R 363 LEU PHE ASN LEU ALA VAL ALA ASP PHE LEU LEU ILE ILE SEQRES 7 R 363 CYS LEU PRO PHE LEU MET ASP ASN TYR VAL ARG ARG TRP SEQRES 8 R 363 ASP TRP LYS PHE GLY ASP ILE PRO CYS ARG LEU MET LEU SEQRES 9 R 363 PHE MET LEU ALA MET ASN ARG GLN GLY SER ILE ILE PHE SEQRES 10 R 363 LEU THR VAL VAL ALA VAL ASP ARG TYR PHE ARG VAL VAL SEQRES 11 R 363 HIS PRO HIS HIS ALA LEU ASN LYS ILE SER ASN ARG THR SEQRES 12 R 363 ALA ALA ILE ILE SER CYS LEU LEU TRP GLY ILE THR ILE SEQRES 13 R 363 GLY LEU THR VAL HIS LEU LEU LYS LYS LYS MET PRO ILE SEQRES 14 R 363 GLN ASN GLY GLY ALA ASN LEU CYS SER SER PHE SER ILE SEQRES 15 R 363 CYS HIS THR PHE GLN TRP HIS GLU ALA MET PHE LEU LEU SEQRES 16 R 363 GLU PHE PHE LEU PRO LEU GLY ILE ILE LEU PHE CYS SER SEQRES 17 R 363 ALA ARG ILE ILE TRP SER LEU ARG GLN ARG GLN MET ASP SEQRES 18 R 363 ARG HIS ALA LYS ILE LYS ARG ALA ILE THR PHE ILE MET SEQRES 19 R 363 VAL VAL ALA ILE VAL PHE VAL ILE CYS PHE LEU PRO SER SEQRES 20 R 363 VAL VAL VAL ARG ILE ARG ILE PHE TRP LEU LEU HIS THR SEQRES 21 R 363 SER GLY THR GLN ASN CYS GLU VAL TYR ARG SER VAL ASP SEQRES 22 R 363 LEU ALA PHE PHE ILE THR LEU SER PHE THR TYR MET ASN SEQRES 23 R 363 SER MET LEU ASP PRO VAL VAL TYR TYR PHE SER SER PRO SEQRES 24 R 363 SER PHE PRO ASN PHE PHE SER THR LEU ILE ASN ARG CYS SEQRES 25 R 363 LEU GLN ARG LYS MET THR GLY GLU PRO ASP ASN ASN ARG SEQRES 26 R 363 SER THR SER VAL GLU LEU THR GLY ASP PRO ASN LYS THR SEQRES 27 R 363 ARG GLY ALA PRO GLU ALA LEU MET ALA ASN SER GLY GLU SEQRES 28 R 363 PRO TRP SER PRO SER TYR LEU GLY PRO THR SER PRO SEQRES 1 A 354 MET GLY CYS THR LEU SER ALA GLU ASP LYS ALA ALA VAL SEQRES 2 A 354 GLU ARG SER LYS MET ILE ASP ARG ASN LEU ARG GLU ASP SEQRES 3 A 354 GLY GLU LYS ALA ALA ARG GLU VAL LYS LEU LEU LEU LEU SEQRES 4 A 354 GLY ALA GLY GLU SER GLY LYS ASN THR ILE VAL LYS GLN SEQRES 5 A 354 MET LYS ILE ILE HIS GLU ALA GLY TYR SER GLU GLU GLU SEQRES 6 A 354 CYS LYS GLN TYR LYS ALA VAL VAL TYR SER ASN THR ILE SEQRES 7 A 354 GLN SER ILE ILE ALA ILE ILE ARG ALA MET GLY ARG LEU SEQRES 8 A 354 LYS ILE ASP PHE GLY ASP SER ALA ARG ALA ASP ASP ALA SEQRES 9 A 354 ARG GLN LEU PHE VAL LEU ALA GLY ALA ALA GLU GLU GLY SEQRES 10 A 354 PHE MET THR ALA GLU LEU ALA GLY VAL ILE LYS ARG LEU SEQRES 11 A 354 TRP LYS ASP SER GLY VAL GLN ALA CYS PHE ASN ARG SER SEQRES 12 A 354 ARG GLU TYR GLN LEU ASN ASP SER ALA ALA TYR TYR LEU SEQRES 13 A 354 ASN ASP LEU ASP ARG ILE ALA GLN PRO ASN TYR ILE PRO SEQRES 14 A 354 THR GLN GLN ASP VAL LEU ARG THR ARG VAL LYS THR THR SEQRES 15 A 354 GLY ILE VAL GLU THR HIS PHE THR PHE LYS ASP LEU HIS SEQRES 16 A 354 PHE LYS MET PHE ASP VAL GLY ALA GLN ARG SER GLU ARG SEQRES 17 A 354 LYS LYS TRP ILE HIS CYS PHE GLU GLY VAL THR ALA ILE SEQRES 18 A 354 ILE PHE CYS VAL ALA LEU SER ASP TYR ASP LEU VAL LEU SEQRES 19 A 354 ALA GLU ASP GLU GLU MET ASN ARG MET HIS ALA SER MET SEQRES 20 A 354 LYS LEU PHE ASP SER ILE CYS ASN ASN LYS TRP PHE THR SEQRES 21 A 354 ASP THR SER ILE ILE LEU PHE LEU ASN LYS LYS ASP LEU SEQRES 22 A 354 PHE GLU GLU LYS ILE LYS LYS SER PRO LEU THR ILE CYS SEQRES 23 A 354 TYR PRO GLU TYR ALA GLY SER ASN THR TYR GLU GLU ALA SEQRES 24 A 354 ALA ALA TYR ILE GLN CYS GLN PHE GLU ASP LEU ASN LYS SEQRES 25 A 354 ARG LYS ASP THR LYS GLU ILE TYR THR HIS PHE THR CYS SEQRES 26 A 354 SER THR ASP THR LYS ASN VAL GLN PHE VAL PHE ASP ALA SEQRES 27 A 354 VAL THR ASP VAL ILE ILE LYS ASN ASN LEU LYS ASP CYS SEQRES 28 A 354 GLY LEU PHE SEQRES 1 B 340 GLN SER GLU LEU ASP GLN LEU ARG GLN GLU ALA GLU GLN SEQRES 2 B 340 LEU LYS ASN GLN ILE ARG ASP ALA ARG LYS ALA CYS ALA SEQRES 3 B 340 ASP ALA THR LEU SER GLN ILE THR ASN ASN ILE ASP PRO SEQRES 4 B 340 VAL GLY ARG ILE GLN MET ARG THR ARG ARG THR LEU ARG SEQRES 5 B 340 GLY HIS LEU ALA LYS ILE TYR ALA MET HIS TRP GLY THR SEQRES 6 B 340 ASP SER ARG LEU LEU VAL SER ALA SER GLN ASP GLY LYS SEQRES 7 B 340 LEU ILE ILE TRP ASP SER TYR THR THR ASN LYS VAL HIS SEQRES 8 B 340 ALA ILE PRO LEU ARG SER SER TRP VAL MET THR CYS ALA SEQRES 9 B 340 TYR ALA PRO SER GLY ASN TYR VAL ALA CYS GLY GLY LEU SEQRES 10 B 340 ASP ASN ILE CYS SER ILE TYR ASN LEU LYS THR ARG GLU SEQRES 11 B 340 GLY ASN VAL ARG VAL SER ARG GLU LEU ALA GLY HIS THR SEQRES 12 B 340 GLY TYR LEU SER CYS CYS ARG PHE LEU ASP ASP ASN GLN SEQRES 13 B 340 ILE VAL THR SER SER GLY ASP THR THR CYS ALA LEU TRP SEQRES 14 B 340 ASP ILE GLU THR GLY GLN GLN THR THR THR PHE THR GLY SEQRES 15 B 340 HIS THR GLY ASP VAL MET SER LEU SER LEU ALA PRO ASP SEQRES 16 B 340 THR ARG LEU PHE VAL SER GLY ALA CYS ASP ALA SER ALA SEQRES 17 B 340 LYS LEU TRP ASP VAL ARG GLU GLY MET CYS ARG GLN THR SEQRES 18 B 340 PHE THR GLY HIS GLU SER ASP ILE ASN ALA ILE CYS PHE SEQRES 19 B 340 PHE PRO ASN GLY ASN ALA PHE ALA THR GLY SER ASP ASP SEQRES 20 B 340 ALA THR CYS ARG LEU PHE ASP LEU ARG ALA ASP GLN GLU SEQRES 21 B 340 LEU MET THR TYR SER HIS ASP ASN ILE ILE CYS GLY ILE SEQRES 22 B 340 THR SER VAL SER PHE SER LYS SER GLY ARG LEU LEU LEU SEQRES 23 B 340 ALA GLY TYR ASP ASP PHE ASN CYS ASN VAL TRP ASP ALA SEQRES 24 B 340 LEU LYS ALA ASP ARG ALA GLY VAL LEU ALA GLY HIS ASP SEQRES 25 B 340 ASN ARG VAL SER CYS LEU GLY VAL THR ASP ASP GLY MET SEQRES 26 B 340 ALA VAL ALA THR GLY SER TRP ASP SER PHE LEU LYS ILE SEQRES 27 B 340 TRP ASN SEQRES 1 C 71 MET ALA SER ASN ASN THR ALA SER ILE ALA GLN ALA ARG SEQRES 2 C 71 LYS LEU VAL GLU GLN LEU LYS MET GLU ALA ASN ILE ASP SEQRES 3 C 71 ARG ILE LYS VAL SER LYS ALA ALA ALA ASP LEU MET ALA SEQRES 4 C 71 TYR CYS GLU ALA HIS ALA LYS GLU ASP PRO LEU LEU THR SEQRES 5 C 71 PRO VAL PRO ALA SER GLU ASN PRO PHE ARG GLU LYS LYS SEQRES 6 C 71 PHE PHE CYS ALA ILE LEU SEQRES 1 E 267 MET VAL GLN LEU VAL GLU SER GLY GLY GLY LEU VAL GLN SEQRES 2 E 267 PRO GLY GLY SER ARG LYS LEU SER CYS SER ALA SER GLY SEQRES 3 E 267 PHE ALA PHE SER SER PHE GLY MET HIS TRP VAL ARG GLN SEQRES 4 E 267 ALA PRO GLU LYS GLY LEU GLU TRP VAL ALA TYR ILE SER SEQRES 5 E 267 SER GLY SER GLY THR ILE TYR TYR ALA ASP THR VAL LYS SEQRES 6 E 267 GLY ARG PHE THR ILE SER ARG ASP ASP PRO LYS ASN THR SEQRES 7 E 267 LEU PHE LEU GLN MET THR SER LEU ARG SER GLU ASP THR SEQRES 8 E 267 ALA MET TYR TYR CYS VAL ARG SER ILE TYR TYR TYR GLY SEQRES 9 E 267 SER SER PRO PHE ASP PHE TRP GLY GLN GLY THR THR LEU SEQRES 10 E 267 THR VAL SER SER GLY GLY GLY GLY SER GLY GLY GLY GLY SEQRES 11 E 267 SER GLY GLY GLY GLY SER ASP ILE VAL MET THR GLN ALA SEQRES 12 E 267 THR SER SER VAL PRO VAL THR PRO GLY GLU SER VAL SER SEQRES 13 E 267 ILE SER CYS ARG SER SER LYS SER LEU LEU HIS SER ASN SEQRES 14 E 267 GLY ASN THR TYR LEU TYR TRP PHE LEU GLN ARG PRO GLY SEQRES 15 E 267 GLN SER PRO GLN LEU LEU ILE TYR ARG MET SER ASN LEU SEQRES 16 E 267 ALA SER GLY VAL PRO ASP ARG PHE SER GLY SER GLY SER SEQRES 17 E 267 GLY THR ALA PHE THR LEU THR ILE SER ARG LEU GLU ALA SEQRES 18 E 267 GLU ASP VAL GLY VAL TYR TYR CYS MET GLN HIS LEU GLU SEQRES 19 E 267 TYR PRO LEU THR PHE GLY ALA GLY THR LYS LEU GLU LEU SEQRES 20 E 267 LYS ALA ALA ALA LEU GLU VAL LEU PHE GLN GLY PRO HIS SEQRES 21 E 267 HIS HIS HIS HIS HIS HIS HIS HET FI7 R 401 28 HETNAM FI7 2-[[2,2-DIMETHYL-3-[3-(5-OXIDANYLPYRIDIN-2-YL)-1,2,4- HETNAM 2 FI7 OXADIAZOL-5-YL]PROPANOYL]AMINO]CYCLOHEXENE-1- HETNAM 3 FI7 CARBOXYLIC ACID FORMUL 6 FI7 C19 H22 N4 O5 HELIX 1 AA1 ASP R 24 PHE R 54 1 31 HELIX 2 AA2 LYS R 60 ILE R 78 1 19 HELIX 3 AA3 CYS R 79 ARG R 89 1 11 HELIX 4 AA4 ASP R 97 HIS R 131 1 35 HELIX 5 AA5 HIS R 134 LYS R 138 5 5 HELIX 6 AA6 SER R 140 VAL R 160 1 21 HELIX 7 AA7 HIS R 161 LYS R 165 5 5 HELIX 8 AA8 GLN R 187 ARG R 218 1 32 HELIX 9 AA9 LYS R 225 SER R 261 1 37 HELIX 10 AB1 CYS R 266 LEU R 280 1 15 HELIX 11 AB2 PHE R 282 TYR R 295 1 14 HELIX 12 AB3 SER A 6 ALA A 31 1 26 HELIX 13 AB4 GLY A 45 LYS A 54 1 10 HELIX 14 AB5 GLU A 207 GLU A 216 5 10 HELIX 15 AB6 ALA A 226 TYR A 230 5 5 HELIX 16 AB7 ASN A 241 ASN A 255 1 15 HELIX 17 AB8 LYS A 270 ILE A 278 1 9 HELIX 18 AB9 PRO A 282 CYS A 286 5 5 HELIX 19 AC1 THR A 295 ASP A 309 1 15 HELIX 20 AC2 THR A 329 LEU A 348 1 20 HELIX 21 AC3 SER B 2 CYS B 25 1 24 HELIX 22 AC4 THR B 29 THR B 34 1 6 HELIX 23 AC5 ASN B 35 ILE B 37 5 3 HELIX 24 AC6 ALA C 7 ASN C 24 1 18 HELIX 25 AC7 LYS C 29 HIS C 44 1 16 HELIX 26 AC8 ALA E 28 PHE E 32 5 5 HELIX 27 AC9 SER E 53 GLY E 56 5 4 HELIX 28 AD1 ARG E 87 THR E 91 5 5 SHEET 1 AA1 3 GLU R 12 ILE R 13 0 SHEET 2 AA1 3 ASN R 17 CYS R 19 -1 O CYS R 18 N GLU R 12 SHEET 3 AA1 3 ILE R 182 CYS R 183 -1 O ILE R 182 N CYS R 19 SHEET 1 AA2 2 ILE R 169 ASN R 171 0 SHEET 2 AA2 2 ALA R 174 LEU R 176 -1 O ALA R 174 N ASN R 171 SHEET 1 AA3 6 VAL A 185 PHE A 191 0 SHEET 2 AA3 6 LEU A 194 ASP A 200 -1 O MET A 198 N THR A 187 SHEET 3 AA3 6 VAL A 34 LEU A 39 1 N LEU A 36 O LYS A 197 SHEET 4 AA3 6 ALA A 220 VAL A 225 1 O ILE A 222 N LEU A 39 SHEET 5 AA3 6 SER A 263 LEU A 268 1 O PHE A 267 N PHE A 223 SHEET 6 AA3 6 ILE A 319 PHE A 323 1 O TYR A 320 N ILE A 264 SHEET 1 AA4 4 ARG B 46 LEU B 51 0 SHEET 2 AA4 4 LEU B 336 ASN B 340 -1 O ILE B 338 N ARG B 48 SHEET 3 AA4 4 VAL B 327 SER B 331 -1 N VAL B 327 O TRP B 339 SHEET 4 AA4 4 VAL B 315 VAL B 320 -1 N CYS B 317 O GLY B 330 SHEET 1 AA5 4 ILE B 58 TRP B 63 0 SHEET 2 AA5 4 LEU B 69 SER B 74 -1 O VAL B 71 N HIS B 62 SHEET 3 AA5 4 LYS B 78 ASP B 83 -1 O TRP B 82 N LEU B 70 SHEET 4 AA5 4 ASN B 88 PRO B 94 -1 O ILE B 93 N LEU B 79 SHEET 1 AA6 4 VAL B 100 TYR B 105 0 SHEET 2 AA6 4 TYR B 111 GLY B 116 -1 O GLY B 115 N MET B 101 SHEET 3 AA6 4 CYS B 121 ASN B 125 -1 O SER B 122 N CYS B 114 SHEET 4 AA6 4 ARG B 134 LEU B 139 -1 O LEU B 139 N CYS B 121 SHEET 1 AA7 4 LEU B 146 PHE B 151 0 SHEET 2 AA7 4 GLN B 156 SER B 161 -1 O VAL B 158 N ARG B 150 SHEET 3 AA7 4 CYS B 166 ASP B 170 -1 O TRP B 169 N ILE B 157 SHEET 4 AA7 4 GLN B 176 PHE B 180 -1 O THR B 177 N LEU B 168 SHEET 1 AA8 4 VAL B 187 LEU B 192 0 SHEET 2 AA8 4 LEU B 198 ALA B 203 -1 O GLY B 202 N MET B 188 SHEET 3 AA8 4 SER B 207 ASP B 212 -1 O TRP B 211 N PHE B 199 SHEET 4 AA8 4 CYS B 218 THR B 223 -1 O PHE B 222 N ALA B 208 SHEET 1 AA9 4 ILE B 229 PHE B 234 0 SHEET 2 AA9 4 ALA B 240 SER B 245 -1 O ALA B 242 N CYS B 233 SHEET 3 AA9 4 CYS B 250 ASP B 254 -1 O PHE B 253 N PHE B 241 SHEET 4 AA9 4 GLN B 259 TYR B 264 -1 O LEU B 261 N LEU B 252 SHEET 1 AB1 4 ILE B 273 PHE B 278 0 SHEET 2 AB1 4 LEU B 284 TYR B 289 -1 O GLY B 288 N SER B 275 SHEET 3 AB1 4 CYS B 294 ASP B 298 -1 O ASN B 295 N ALA B 287 SHEET 4 AB1 4 ARG B 304 LEU B 308 -1 O ALA B 305 N VAL B 296 SHEET 1 AB2 4 GLN E 3 SER E 7 0 SHEET 2 AB2 4 ARG E 18 SER E 25 -1 O SER E 23 N VAL E 5 SHEET 3 AB2 4 THR E 78 MET E 83 -1 O LEU E 81 N LEU E 20 SHEET 4 AB2 4 PHE E 68 ASP E 73 -1 N ASP E 73 O THR E 78 SHEET 1 AB3 6 GLY E 10 VAL E 12 0 SHEET 2 AB3 6 THR E 115 VAL E 119 1 O THR E 118 N GLY E 10 SHEET 3 AB3 6 ALA E 92 SER E 99 -1 N ALA E 92 O LEU E 117 SHEET 4 AB3 6 GLY E 33 GLN E 39 -1 N VAL E 37 O TYR E 95 SHEET 5 AB3 6 LEU E 45 ILE E 51 -1 O GLU E 46 N ARG E 38 SHEET 6 AB3 6 ILE E 58 TYR E 60 -1 O TYR E 59 N TYR E 50 SHEET 1 AB4 4 GLY E 10 VAL E 12 0 SHEET 2 AB4 4 THR E 115 VAL E 119 1 O THR E 118 N GLY E 10 SHEET 3 AB4 4 ALA E 92 SER E 99 -1 N ALA E 92 O LEU E 117 SHEET 4 AB4 4 PHE E 110 TRP E 111 -1 O PHE E 110 N ARG E 98 SHEET 1 AB5 4 MET E 140 THR E 141 0 SHEET 2 AB5 4 VAL E 155 SER E 161 -1 O ARG E 160 N THR E 141 SHEET 3 AB5 4 ALA E 211 ILE E 216 -1 O LEU E 214 N ILE E 157 SHEET 4 AB5 4 PHE E 203 SER E 208 -1 N SER E 206 O THR E 213 SHEET 1 AB6 6 SER E 146 PRO E 148 0 SHEET 2 AB6 6 THR E 243 GLU E 246 1 O LYS E 244 N VAL E 147 SHEET 3 AB6 6 VAL E 226 GLN E 231 -1 N TYR E 227 O THR E 243 SHEET 4 AB6 6 LEU E 174 GLN E 179 -1 N TYR E 175 O MET E 230 SHEET 5 AB6 6 GLN E 186 TYR E 190 -1 O LEU E 188 N TRP E 176 SHEET 6 AB6 6 ASN E 194 LEU E 195 -1 O ASN E 194 N TYR E 190 SSBOND 1 CYS R 18 CYS R 183 1555 1555 2.04 SSBOND 2 CYS R 19 CYS R 266 1555 1555 2.04 SSBOND 3 CYS R 100 CYS R 177 1555 1555 2.03 SSBOND 4 CYS E 159 CYS E 229 1555 1555 2.04 CISPEP 1 TYR E 235 PRO E 236 0 1.60 CRYST1 1.000 1.000 1.000 90.00 90.00 90.00 P 1 ORIGX1 1.000000 0.000000 0.000000 0.00000 ORIGX2 0.000000 1.000000 0.000000 0.00000 ORIGX3 0.000000 0.000000 1.000000 0.00000 SCALE1 1.000000 0.000000 0.000000 0.00000 SCALE2 0.000000 1.000000 0.000000 0.00000 SCALE3 0.000000 0.000000 1.000000 0.00000