Structure of PDB 5a8y Chain A Binding Site BS02

Receptor Information
>5a8y Chain A (length=216) Species: 9606 (Homo sapiens) [Search protein sequence] [Download receptor structure] [Download structure with residue number starting from 1] [View receptor structure]
IVGGRRARPHAWPFMVSLQLRGGHFCGATLIAPNFVMSAAHCVANVNVRA
VRVVLGAHNLSRREPTRQVFAVQRIFENGYDPVNLLNDIVILQLNGSATI
NANVQVAQLPAQGRRLGNGVQCLAMGWGLLGRGIASVLQELNVTVVTSLC
RRSNVCTLVRGRQAGVCFGDSGSPLVCNGLIHGIASFVRGGCASGLYPDA
FAPVAQFVNWIDSIIQ
Ligand information
Ligand IDVBM
InChIInChI=1S/C23H16F3N7O2/c1-13-18(12-28)19(15-8-6-14(11-27)7-9-15)33-21(29-20(31-33)30-22(34)35-2)32(13)17-5-3-4-16(10-17)23(24,25)26/h3-10,19H,1-2H3,(H,30,31,34)/t19-/m1/s1
InChIKeyCBMCUAQNNUOHFF-LJQANCHMSA-N
SMILES
SoftwareSMILES
CACTVS 3.385COC(=O)N=C1NN2[C@H](c3ccc(cc3)C#N)C(=C(C)N(c4cccc(c4)C(F)(F)F)C2=N1)C#N
OpenEye OEToolkits 1.7.6CC1=C(C(N2C(=NC(=NC(=O)OC)N2)N1c3cccc(c3)C(F)(F)F)c4ccc(cc4)C#N)C#N
OpenEye OEToolkits 1.7.6CC1=C([C@H](N2C(=N/C(=N/C(=O)OC)/N2)N1c3cccc(c3)C(F)(F)F)c4ccc(cc4)C#N)C#N
CACTVS 3.385COC(=O)N=C1NN2[CH](c3ccc(cc3)C#N)C(=C(C)N(c4cccc(c4)C(F)(F)F)C2=N1)C#N
FormulaC23 H16 F3 N7 O2
NameMETHYL {(7R)-6-CYANO-7-(4-CYANOPHENYL)-5-METHYL-4-[3-(TRIFLUOROMETHYL)PHENYL]-4,7-DIHYDRO[1,2,4]TRIAZOLO[1,5-A]PYRIMIDIN-2-YL}CARBAMATE
ChEMBL
DrugBank
ZINCZINC000168554873
PDB chain5a8y Chain A Residue 1001 [Download ligand structure] [Download structure with residue number starting from 1] [View ligand structure]
Receptor-Ligand Complex Structure
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PDB5a8y Potent and Selective Human Neutrophil Elastase Inhibitors with Novel Equatorial Ring Topology: In Vivo Efficacy of the Polar Pyrimidopyridazine Bay-8040 in a Pulmonary Arterial Hypertension Rat Model.
Resolution1.9 Å
Binding residue
(original residue number in PDB)		H57 Y94 L99 D102 V190 C191 F192 S195 A213 S214 F215 V216 R217
Binding residue
(residue number reindexed from 1)		H41 Y80 L85 D88 V166 C167 F168 S171 A185 S186 F187 V188 R189
Annotation score1
Binding affinityMOAD: ic50=0.17nM
PDBbind-CN: -logKd/Ki=9.77,IC50=0.17nM
Enzymatic activity
Catalytic site (original residue number in PDB) H57 D102 G189 C191 F192 G193 D194 S195 G196
Catalytic site (residue number reindexed from 1) H41 D88 G165 C167 F168 G169 D170 S171 G172
Enzyme Commision number 3.4.21.37: leukocyte elastase.
Gene Ontology
Molecular Function
GO:0002020 protease binding
GO:0003714 transcription corepressor activity
GO:0004175 endopeptidase activity
GO:0004252 serine-type endopeptidase activity
GO:0005515 protein binding
GO:0008201 heparin binding
GO:0008233 peptidase activity
GO:0008236 serine-type peptidase activity
GO:0019955 cytokine binding
Biological Process
GO:0000122 negative regulation of transcription by RNA polymerase II
GO:0001878 response to yeast
GO:0002438 acute inflammatory response to antigenic stimulus
GO:0002523 leukocyte migration involved in inflammatory response
GO:0002812 biosynthetic process of antibacterial peptides active against Gram-negative bacteria
GO:0006508 proteolysis
GO:0006874 intracellular calcium ion homeostasis
GO:0006909 phagocytosis
GO:0009411 response to UV
GO:0022617 extracellular matrix disassembly
GO:0030163 protein catabolic process
GO:0032496 response to lipopolysaccharide
GO:0032682 negative regulation of chemokine production
GO:0032717 negative regulation of interleukin-8 production
GO:0032757 positive regulation of interleukin-8 production
GO:0042742 defense response to bacterium
GO:0043406 positive regulation of MAP kinase activity
GO:0048661 positive regulation of smooth muscle cell proliferation
GO:0050728 negative regulation of inflammatory response
GO:0050778 positive regulation of immune response
GO:0050832 defense response to fungus
GO:0050900 leukocyte migration
GO:0050922 negative regulation of chemotaxis
GO:0070269 pyroptotic inflammatory response
GO:0070945 neutrophil-mediated killing of gram-negative bacterium
GO:0070947 neutrophil-mediated killing of fungus
GO:1903238 positive regulation of leukocyte tethering or rolling
Cellular Component
GO:0005576 extracellular region
GO:0005615 extracellular space
GO:0005737 cytoplasm
GO:0005829 cytosol
GO:0009986 cell surface
GO:0017053 transcription repressor complex
GO:0030141 secretory granule
GO:0031410 cytoplasmic vesicle
GO:0035578 azurophil granule lumen
GO:0035580 specific granule lumen
GO:0045335 phagocytic vesicle
GO:0062023 collagen-containing extracellular matrix
GO:0070062 extracellular exosome

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Molecular Function
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Biological Process
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Cellular Component
External links
PDB RCSB:5a8y, PDBe:5a8y, PDBj:5a8y
PDBsum5a8y
PubMed26333652
UniProtP08246|ELNE_HUMAN Neutrophil elastase (Gene Name=ELANE)

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