Structure of PDB 1h7x Chain C Binding Site BS07

Receptor Information

>1h7x Chain C (length=1019) Species: 9823 (Sus scrofa)

APVLSKDVADIESILALNPRTQSHAALHSTLAKKLDKKHWKRNPDKNCFH
CEKLENNFDDIKHTTLGERGALREAMRCLKCADAPCQKSCPTHLDIKSFI
TSISNKNYYGAAKMIFSDNPLGLTCGMVCPTSDLCVGGCNLYATEEGSIN
IGGLQQFASEVFKAMNIPQIRNPCLPSQEKMPEAYSAKIALLGAGPASIS
CASFLARLGYSDITIFEKQEYVGGLSTSEIPQFRLPYDVVNFEIELMKDL
GVKIICGKSLSENEITLNTLKEEGYKAAFIGIGLPEPKTDDIFQGLTQDQ
GFYTSKDFLPLVAKSSKAGMCACHSPLPSIRGAVIVLGAGDTAFDCATSA
LRCGARRVFLVFRKGFVNIRAVPEEVELAKEEKCEFLPFLSPRKVIVKGG
RIVAVQFVRTEQDETGKWNEDEDQIVHLKADVVISAFGSVLRDPKVKEAL
SPIKFNRWDLPEVDPETMQTSEPWVFAGGDIVGMANTTVESVNDGKQASW
YIHKYIQAQYGASVSAKPELPLFYTPVDLVDISVEMAGLKFINPFGLASA
APTTSSSMIRRAFEAGWGFALTKTFSLDKDIVTNVSPRIVRGTTSGPMYG
PGQSSFLNIELISEKTAAYWCQSVTELKADFPDNIVIASIMCSYNKNDWM
ELSRKAEASGADALELNLSAPHGMGERGMGLACGQDPELVRNICRWVRQA
VQIPFFAKLTPNVTDIVSIARAAKEGGADGVTATNTVSGLMGLKADGTPW
PAVGAGKRTTYGGVSGTAIRPIALRAVTTIARALPGFPILATGGIDSAES
GLQFLHSGASVLQVCSAVQNQDFTVIQDYCTGLKALLYLKSIEELQGWDG
QSPGTESHQKGKPVPRIAELMGKKLPNFGPYLEQRKKIIAEEKMRLKEQN
AAFPPLERKPFIPKKPIPAIKDVIGKALQYLGTFGELSNIEQVVAVIDEE
MCINCGKCYMTCNDSGYQAIQFDPETHLPTVTDTCTGCTLCLSVCPIIDC
IRMVSRTTPYEPKRGLPLA

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: 1h7x Chain C Residue 1032

Receptor-Ligand Complex Structure

Structure summary

• PDB: 1h7x Crystal Structure of Dihydropyrimidine Dehydrogenase, a Major Determinant of the Pharmacokinetics of the Anti-Cancer Drug 5-Fluorouracil
• Resolution: 2.01 Å
• Binding residue (original residue number in PDB): A340 G341 T343 R364 K365 R371 A437 F438 G439 G484 M485 A486 N487
• Binding residue (residue number reindexed from 1): A339 G340 T342 R363 K364 R370 A436 F437 G438 G483 M484 A485 N486
• Annotation score: 4

Enzymatic activity

• Catalytic site (original residue number in PDB): K574 G601 S605 A671 H673 G674 K709 T735
• Catalytic site (residue number reindexed from 1): K573 G600 S604 A670 H672 G673 K708 T734
• Enzyme Commision number: 1.3.1.2: dihydropyrimidine dehydrogenase (NADP(+)).

Gene Ontology

Molecular Function

• GO:0000166 nucleotide binding
• GO:0002058 uracil binding
• GO:0010181 FMN binding
• GO:0016491 oxidoreductase activity
• GO:0016627 oxidoreductase activity, acting on the CH-CH group of donors
• GO:0017113 dihydropyrimidine dehydrogenase (NADP+) activity
• GO:0042803 protein homodimerization activity
• GO:0046872 metal ion binding
• GO:0050660 flavin adenine dinucleotide binding
• GO:0050661 NADP binding
• GO:0051536 iron-sulfur cluster binding
• GO:0051539 4 iron, 4 sulfur cluster binding

Biological Process

• GO:0006210 thymine catabolic process
• GO:0006212 uracil catabolic process
• GO:0006214 thymidine catabolic process
• GO:0019483 beta-alanine biosynthetic process

Cellular Component

• GO:0005737 cytoplasm
• GO:0005829 cytosol

External links

• PDB: RCSB:1h7x, PDBe:1h7x, PDBj:1h7x
• PDBsum: 1h7x
• PubMed: 11179210
• UniProt: Q28943|DPYD_PIG Dihydropyrimidine dehydrogenase [NADP(+)] (Gene Name=DPYD)