Structure of PDB 3fh7 Chain A Binding Site BS02

Receptor Information

>3fh7 Chain A (length=607) Species: 9606 (Homo sapiens)

VDTCSLASPASVCRTKHLHLRCSVDFTRRTLTGTAALTVQSQEDNLRSLV
LDTKDLTIEKVVINGQEVKYALGERQSYKGSPMEISLPIALSKNQEIVIE
ISFETSPKSSALQWLTPEQTSGKEHPYLFSQCQAIHCRAILPCQDTPSVK
LTYTAEVSVPKELVALMSAIRDGETPDPEDPSRKIYKFIQKVPIPCYLIA
LVVGALESRQIGPRTLVWSEKEQVEKSAYEFSETESMLKIAEDLGGPYVW
GQYDLLVLPPSFPYGGMENPCLTFVTPTLLAGDKSLSNVIAHEISHSWTG
NLVTNKTWDHFWLNEGHTVYLERHICGRLFGEKFRHFNALGGWGELQNSV
KTFGETHPFTKLVVDLTDIDPDVAYSSVPYEKGFALLFYLEQLLGGPEIF
LGFLKAYVEKFSYKSITTDDWKDFLYSYFKDKVDVLNQVDWNAWLYSPGL
PPIKPNYDMTLTNACIALSQRWITAKEDDLNSFNATDLKDLSSHQLNEFL
AQTLQRAPLPLGHIKRMQEVYNFNAINNSEIRFRWLRLCIQSKWEDAIPL
ALKMATEQGRMKFTRPLFKDLAAFDKSHDQAVRTYQEHKASMHPVTAMLV
GKDLKVD

Ligand information

• Ligand ID: 25P
• InChI: InChI=1S/C21H24ClNO4/c22-16-5-7-19(8-6-16)27-20-11-9-18(10-12-20)26-15-17-3-1-13-23(17)14-2-4-21(24)25/h5-12,17H,1-4,13-15H2,(H,24,25)/p-1/t17-/m0/s1
• InChIKey: PVCTYSQBVIGZRU-KRWDZBQOSA-M
• SMILES:
  OpenEye OEToolkits 1.5.0: c1cc(ccc1OC[C@@H]2CCC[N@@]2CCCC(=O)[O-])Oc3ccc(cc3)Cl
  CACTVS 3.341: [O-]C(=O)CCCN1CCC[CH]1COc2ccc(Oc3ccc(Cl)cc3)cc2
  OpenEye OEToolkits 1.5.0: c1cc(ccc1OCC2CCCN2CCCC(=O)[O-])Oc3ccc(cc3)Cl
  ACDLabs 10.04: Clc3ccc(Oc2ccc(OCC1N(CCCC([O-])=O)CCC1)cc2)cc3
  CACTVS 3.341: [O-]C(=O)CCCN1CCC[C@H]1COc2ccc(Oc3ccc(Cl)cc3)cc2
• Formula: C21 H23 Cl N O4
• Name: 4-[(2S)-2-{[4-(4-chlorophenoxy)phenoxy]methyl}pyrrolidin-1-yl]butanoate
• PDB chain: 3fh7 Chain A Residue 612

Receptor-Ligand Complex Structure

Structure summary

• PDB: 3fh7 Discovery of 4-[(2S)-2-{[4-(4-chlorophenoxy)phenoxy]methyl}-1-pyrrolidinyl]butanoic acid (DG-051) as a novel leukotriene A4 hydrolase inhibitor of leukotriene B4 biosynthesis.
• Resolution: 2.05 Å
• Binding residue (original residue number in PDB): Q134 Q136 A137 Y267 G269 M270 E271 H295 E296 H299 W311 F314 E318 V367 L369 P374 Y378 Y383
• Binding residue (residue number reindexed from 1): Q131 Q133 A134 Y264 G266 M267 E268 H292 E293 H296 W308 F311 E315 V364 L366 P371 Y375 Y380
• Annotation score: 1
• Binding affinity: MOAD: Kd=25nM
  PDBbind-CN: -logKd/Ki=7.60,Kd=25nM

Enzymatic activity

• Catalytic site (original residue number in PDB): E271 H295 E296 H299 E318 D375 Y383
• Catalytic site (residue number reindexed from 1): E268 H292 E293 H296 E315 D372 Y380
• Enzyme Commision number: 3.3.2.6: leukotriene-A4 hydrolase.
  3.4.11.4: tripeptide aminopeptidase.

Gene Ontology

Molecular Function

• GO:0003723 RNA binding
• GO:0004177 aminopeptidase activity
• GO:0004301 epoxide hydrolase activity
• GO:0004463 leukotriene-A4 hydrolase activity
• GO:0005515 protein binding
• GO:0008233 peptidase activity
• GO:0008237 metallopeptidase activity
• GO:0008270 zinc ion binding
• GO:0045148 tripeptide aminopeptidase activity
• GO:0046872 metal ion binding
• GO:0070006 metalloaminopeptidase activity

Biological Process

• GO:0006508 proteolysis
• GO:0006629 lipid metabolic process
• GO:0006691 leukotriene metabolic process
• GO:0010043 response to zinc ion
• GO:0019370 leukotriene biosynthetic process
• GO:0019538 protein metabolic process
• GO:0043171 peptide catabolic process
• GO:0043434 response to peptide hormone
• GO:0060509 type I pneumocyte differentiation

Cellular Component

• GO:0005576 extracellular region
• GO:0005634 nucleus
• GO:0005654 nucleoplasm
• GO:0005737 cytoplasm
• GO:0005829 cytosol
• GO:0070062 extracellular exosome
• GO:1904724 tertiary granule lumen
• GO:1904813 ficolin-1-rich granule lumen

External links

• PDB: RCSB:3fh7, PDBe:3fh7, PDBj:3fh7
• PDBsum: 3fh7
• PubMed: 19950900
• UniProt: P09960|LKHA4_HUMAN Leukotriene A-4 hydrolase (Gene Name=LTA4H)