Structure of PDB 6y5m Chain A Binding Site BS04

Receptor Information

>6y5m Chain A (length=783) Species: 10090 (Mus musculus)

WTNTSGSCKGRCFELQEVGPPDCRCDNLCKSYSSCCHDFDELCLKTARGW
ECTKDRCGERNEENACHCSEDCLSRGDCCTNYQVVCKGESHWVDDDCEEI
RVPECPAGFVRPPLIIFSVDGFRASYMKKGSKVMPNIEKLRSCGTHAPYM
RPVYPTKTFPNLYTLATGLYPESHGIVGNSMYDPVFDATFHLRGREKFNH
RWWGGQPLWITATKQGVRAGTFFWSVSIPHERRILTILQWLSLPDNERPS
VYAFYSEQPDFSGHKYGPFGPEMTNPLREIDKTVGQLMDGLKQLKLHRCV
NVIFVGDHGMEDVTCDRTEFLSNYLTNVDDITLVPGTLGRIRPKIPNNLK
YDPKAIIANLTCKKPDQHFKPYMKQHLPKRLHYANNRRIEDLHLLVERRW
HVARKPLDKCFFQGDHGFDNKVNSMQTVFVGYGPTFKYRTKVPPFENIEL
YNVMCDLLGLKPAPNNGTHGSLNHLLRTNTFRPTLPEEVSRPNYPGIMYL
QSDFDLGCTCTKGSTEERHLLYGRPAVLYRTSYDILYHTDFESGYSEIFL
MPLWTSYTISKQAEVSSIPEHLTNCVRPDVRVSPGFSQNCLAYKNDKQMS
YGFLFPPYLSSSPEAKYDAFLVTNMVPMYPAFKRVWTYFQRVLVKKYASE
RNGVNVISGPIFDYNYNGLRDIEDEIKQYVEGSSIPVPTHYYSIITSCLD
FTQPADKCDGPLSVSSFILPHRPDNDESCNSSEDESKWVEELMKMHTARV
RDIEHLTGLDFYRKTSRSYSEILTLKTYLHTYE

Ligand information

• Ligand ID: O9W
• InChI: InChI=1S/C24H26ClFN6O/c1-17-14-30(15-19-3-8-23(26)9-4-19)11-12-31(17)24(33)10-6-20-5-7-22(25)13-21(20)16-32-28-18(2)27-29-32/h3-10,13,17H,11-12,14-16H2,1-2H3/b10-6+/t17-/m1/s1
• InChIKey: VZLIOCMTERNIPD-DKISHCGFSA-N
• SMILES:
  CACTVS 3.385: C[C@@H]1CN(CCN1C(=O)/C=C/c2ccc(Cl)cc2Cn3nnc(C)n3)Cc4ccc(F)cc4
  OpenEye OEToolkits 2.0.7: Cc1nnn(n1)Cc2cc(ccc2/C=C/C(=O)N3CCN(C[C@H]3C)Cc4ccc(cc4)F)Cl
  CACTVS 3.385: C[CH]1CN(CCN1C(=O)C=Cc2ccc(Cl)cc2Cn3nnc(C)n3)Cc4ccc(F)cc4
  OpenEye OEToolkits 2.0.7: Cc1nnn(n1)Cc2cc(ccc2C=CC(=O)N3CCN(CC3C)Cc4ccc(cc4)F)Cl
• Formula: C24 H26 Cl F N6 O
• Name: (~{E})-3-[4-chloranyl-2-[(5-methyl-1,2,3,4-tetrazol-2-yl)methyl]phenyl]-1-[(2~{R})-4-[(4-fluorophenyl)methyl]-2-methyl-piperazin-1-yl]prop-2-en-1-one
• ChEMBL: CHEMBL4790845
• PDB chain: 6y5m Chain A Residue 913

Receptor-Ligand Complex Structure

Structure summary

• PDB: 6y5m Development of autotaxin inhibitors: A series of tetrazole cinnamides.
• Resolution: 2.011 Å
• Binding residue (original residue number in PDB): S169 F210 L213 Y214 K248 W254 F273 F274 W275 Y306
• Binding residue (residue number reindexed from 1): S118 F159 L162 Y163 K197 W203 F222 F223 W224 Y255
• Annotation score: 1
• Binding affinity: MOAD: ic50=9.6nM

Enzymatic activity

• Enzyme Commision number: 3.1.4.39: alkylglycerophosphoethanolamine phosphodiesterase.

Gene Ontology

Molecular Function

• GO:0003676 nucleic acid binding
• GO:0004528 phosphodiesterase I activity
• GO:0004551 dinucleotide phosphatase activity
• GO:0004622 lysophospholipase activity
• GO:0004630 phospholipase D activity
• GO:0005044 scavenger receptor activity
• GO:0005509 calcium ion binding
• GO:0008270 zinc ion binding
• GO:0016787 hydrolase activity
• GO:0016788 hydrolase activity, acting on ester bonds
• GO:0030247 polysaccharide binding
• GO:0046872 metal ion binding
• GO:0047391 alkylglycerophosphoethanolamine phosphodiesterase activity

Biological Process

• GO:0006644 phospholipid metabolic process
• GO:0006935 chemotaxis
• GO:0006955 immune response
• GO:0009395 phospholipid catabolic process
• GO:0010634 positive regulation of epithelial cell migration
• GO:0016042 lipid catabolic process
• GO:0016192 vesicle-mediated transport
• GO:0030149 sphingolipid catabolic process
• GO:0030334 regulation of cell migration
• GO:0034638 phosphatidylcholine catabolic process
• GO:0050731 positive regulation of peptidyl-tyrosine phosphorylation
• GO:2000394 positive regulation of lamellipodium morphogenesis

Cellular Component

• GO:0005576 extracellular region
• GO:0005615 extracellular space
• GO:0005886 plasma membrane

External links

• PDB: RCSB:6y5m, PDBe:6y5m, PDBj:6y5m
• PDBsum: 6y5m
• PubMed: 33160025
• UniProt: Q9R1E6|ENPP2_MOUSE Autotaxin (Gene Name=Enpp2)