Structure of PDB 4piv Chain A Binding Site BS01

Receptor Information

>4piv Chain A (length=610) Species: 9606 (Homo sapiens)

MQVPILEKFCFTPHTEEGCLSERAALQEELQLCKGLVQALQTPSQQELPR
LLSAACRLAQVLAQERPKLPEDPLLSGLLDSPALKACLDTAVENMPSLKM
KVVEVLAGHGHLYSRIPGLLSPHPLLQLSYTATDRHPQALEAAQAELQQH
DVAQGQWDPADPAPSALGSADLLVCNCAVAALGDPASALSNMVAALREGG
FLLLHTLLRGHPLGDIVAFLTSQGILSQDAWESLFSRVSLRLVGLKKSFY
GSTLFLCRRPTPQDSPIFLPVDDTSFRWVESLKGILADEDSARPVWLKAI
NCATSGVVGLVNCLRREPGGNRLRCVLLSNLSSTSHVPEVDPGSAELQKV
LQGDLVMNVYRDGAWGAFRHFLLEEDSKTFCPAHKSYIIAGGLGGFGLEL
AQWLIQRGVQKLVLTSRSGIRTGYQAKQVRRWRRQGVQVQVSTSNISSLE
GARGLIAEAAQLGPVGGVFNLAVVLRDGLLENQTPEFFQDVCKPKYSGTL
NLDRVTREACPELDYFVVFSSVSCGRGNAGQSNYGFANSAMERICEKRRH
EGLPGLAVQWGAIGDVGILVETNDTIVSGTLPQRMASCLEVLDLFLNQPH
MVLSSFVLAE

Ligand information

• Ligand ID: NDP
• InChI: InChI=1S/C21H30N7O17P3/c22-17-12-19(25-7-24-17)28(8-26-12)21-16(44-46(33,34)35)14(30)11(43-21)6-41-48(38,39)45-47(36,37)40-5-10-13(29)15(31)20(42-10)27-3-1-2-9(4-27)18(23)32/h1,3-4,7-8,10-11,13-16,20-21,29-31H,2,5-6H2,(H2,23,32)(H,36,37)(H,38,39)(H2,22,24,25)(H2,33,34,35)/t10-,11-,13-,14-,15-,16-,20-,21-/m1/s1
• InChIKey: ACFIXJIJDZMPPO-NNYOXOHSSA-N
• SMILES:
  OpenEye OEToolkits 1.5.0: c1nc(c2c(n1)n(cn2)[C@H]3[C@@H]([C@@H]([C@H](O3)CO[P@](=O)(O)O[P@@](=O)(O)OC[C@@H]4[C@H]([C@H]([C@@H](O4)N5C=CCC(=C5)C(=O)N)O)O)O)OP(=O)(O)O)N
  CACTVS 3.341: NC(=O)C1=CN(C=CC1)[CH]2O[CH](CO[P](O)(=O)O[P](O)(=O)OC[CH]3O[CH]([CH](O[P](O)(O)=O)[CH]3O)n4cnc5c(N)ncnc45)[CH](O)[CH]2O
  CACTVS 3.341: NC(=O)C1=CN(C=CC1)[C@@H]2O[C@H](CO[P@@](O)(=O)O[P@](O)(=O)OC[C@H]3O[C@H]([C@H](O[P](O)(O)=O)[C@@H]3O)n4cnc5c(N)ncnc45)[C@@H](O)[C@H]2O
  OpenEye OEToolkits 1.5.0: c1nc(c2c(n1)n(cn2)C3C(C(C(O3)COP(=O)(O)OP(=O)(O)OCC4C(C(C(O4)N5C=CCC(=C5)C(=O)N)O)O)O)OP(=O)(O)O)N
• Formula: C21 H30 N7 O17 P3
• Name: NADPH DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE
• ChEMBL: CHEMBL407009
• DrugBank: DB02338
• ZINC: ZINC000008215411
• PDB chain: 4piv Chain A Residue 2202

Receptor-Ligand Complex Structure

Structure summary

• PDB: 4piv A human fatty acid synthase inhibitor binds beta-ketoacyl reductase in the keto-substrate site.
• Resolution: 2.299 Å
• Binding residue (original residue number in PDB): G1891 G1894 G1895 F1896 S1916 R1917 S1918 N1945 L1971 A1972 V1973 V1974 K1995 Y2034 W2060 G2061 I2063 G2067 I2068 L2069
• Binding residue (residue number reindexed from 1): G391 G394 G395 F396 S416 R417 S418 N445 L471 A472 V473 V474 K495 Y534 W560 G561 I563 G567 I568 L569
• Annotation score: 4

Enzymatic activity

• Catalytic site (original residue number in PDB): K1995 S2021 Y2034 N2038
• Catalytic site (residue number reindexed from 1): K495 S521 Y534 N538
• Enzyme Commision number: 1.1.1.100: 3-oxoacyl-[acyl-carrier-protein] reductase.
  1.3.1.39: enoyl-[acyl-carrier-protein] reductase (NADPH, Re-specific).
  2.3.1.38: [acyl-carrier-protein] S-acetyltransferase.
  2.3.1.39: [acyl-carrier-protein] S-malonyltransferase.
  2.3.1.41: beta-ketoacyl-[acyl-carrier-protein] synthase I.
  2.3.1.85: fatty-acid synthase system.
  3.1.2.14: oleoyl-[acyl-carrier-protein] hydrolase.
  4.2.1.59: 3-hydroxyacyl-[acyl-carrier-protein] dehydratase.

External links

• PDB: RCSB:4piv, PDBe:4piv, PDBj:4piv
• PDBsum: 4piv
• PubMed: 25086508
• UniProt: P49327|FAS_HUMAN Fatty acid synthase (Gene Name=FASN)