Structure of PDB 1r1i Chain A Binding Site BS02

Receptor Information
>1r1i Chain A (length=696) Species: 9606 (Homo sapiens) [Search protein sequence] [Download receptor structure] [Download structure with residue number starting from 1] [View receptor structure]
GICKSSDCIKSAARLIQNMDATTEPCTDFFKYACGGWLKRNVIPETSSRY
GNFDILRDELEVVLKDVLQEPKTEDIVAVQKAKALYRSCINESAIDSRGG
EPLLKLLPDIYGWPVATENWEQKYGASWTAEKAIAQLNSKYGKKVLINLF
VGTDDKNSVNHVIHIDQPRLGLPSRDYYECTGIYKEACTAYVDFMISVAR
LIRQEERLPIDENQLALEMNKVMELEKEIANATAKPEDRNDPMLLYNKMT
LAQIQNNFSLEINGKPFSWLNFTNEIMSTVNISITNEEDVVVYAPEYLTK
LKPILTKYSARDLQNLMSWRFIMDLVSSLSRTYKESRNAFRKALYGTTSE
TATWRRCANYVNGNMENAVGRLYVEAAFAGESKHVVEDLIAQIREVFIQT
LDDLTWMDAETKKRAEEKALAIKERIGYPDDIVSNDNKLNNEYLELNYKE
DEYFENIIQNLKFSQSKQLKKLREKVDKDEWISGAAVVNAFYSSGRNQIV
FPAGILQPPFFSAQQSNSLNYGGIGMVIGHEITHGFDDNGRNFNKDGDLV
DWWTQQSASNFKEQSQCMVYQYGNFSWDLAGGQHLNGINTLGENIADNGG
LGQAYRAYQNYIKKNGEEKLLPGLDLNHKQLFFLNFAQVWCGTYRPEYAV
NSIKTDVHSPGNFRIIGTLQNSAEFSEAFHCRKNSYMNPEKKCRVW
Ligand information
Ligand IDTI1
InChIInChI=1S/C19H28N2O4S/c1-3-4-6-11-16(26)18(23)21-15(12-14-9-7-5-8-10-14)17(22)20-13(2)19(24)25/h5,7-10,13,15-16,26H,3-4,6,11-12H2,1-2H3,(H,20,22)(H,21,23)(H,24,25)/t13-,15-,16-/m0/s1
InChIKeyGOIYKVXXGCPHQU-BPUTZDHNSA-N
SMILES
SoftwareSMILES
CACTVS 3.341CCCCC[CH](S)C(=O)N[CH](Cc1ccccc1)C(=O)N[CH](C)C(O)=O
ACDLabs 10.04O=C(O)C(NC(=O)C(NC(=O)C(S)CCCCC)Cc1ccccc1)C
OpenEye OEToolkits 1.5.0CCCCCC(C(=O)NC(Cc1ccccc1)C(=O)NC(C)C(=O)O)S
OpenEye OEToolkits 1.5.0CCCCC[C@@H](C(=O)N[C@@H](Cc1ccccc1)C(=O)N[C@@H](C)C(=O)O)S
CACTVS 3.341CCCCC[C@H](S)C(=O)N[C@@H](Cc1ccccc1)C(=O)N[C@@H](C)C(O)=O
FormulaC19 H28 N2 O4 S
Name[2(R,S)-2-SULFANYLHEPTANOYL]-PHE-ALA
ChEMBL
DrugBankDB02597
ZINCZINC000006352218
PDB chain1r1i Chain A Residue 2001 [Download ligand structure] [Download structure with residue number starting from 1] [View ligand structure]
Receptor-Ligand Complex Structure
Global viewLocal viewStructure summary

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PDB1r1i Structural analysis of neprilysin with various specific and potent inhibitors.
Resolution2.6 Å
Binding residue
(original residue number in PDB)		F106 N542 A543 M579 V580 H583 E584 H587 E646 W693 H711 R717
Binding residue
(residue number reindexed from 1)		F53 N489 A490 M526 V527 H530 E531 H534 E593 W640 H658 R664
Annotation score1
Binding affinityPDBbind-CN: -logKd/Ki=8.54,Ki=2.9nM
Enzymatic activity
Catalytic site (original residue number in PDB) H583 E584 H587 E646 D650 H711 R717
Catalytic site (residue number reindexed from 1) H530 E531 H534 E593 D597 H658 R664
Enzyme Commision number 3.4.24.11: neprilysin.
Gene Ontology
Molecular Function
GO:0001786 phosphatidylserine binding
GO:0004175 endopeptidase activity
GO:0004222 metalloendopeptidase activity
GO:0005515 protein binding
GO:0008233 peptidase activity
GO:0008237 metallopeptidase activity
GO:0008238 exopeptidase activity
GO:0008270 zinc ion binding
GO:0042277 peptide binding
GO:0042803 protein homodimerization activity
GO:0046872 metal ion binding
GO:0070012 oligopeptidase activity
GO:1901612 cardiolipin binding
Biological Process
GO:0001822 kidney development
GO:0001890 placenta development
GO:0006508 proteolysis
GO:0006518 peptide metabolic process
GO:0007611 learning or memory
GO:0010814 substance P catabolic process
GO:0010815 bradykinin catabolic process
GO:0016485 protein processing
GO:0019233 sensory perception of pain
GO:0030163 protein catabolic process
GO:0030324 lung development
GO:0042447 hormone catabolic process
GO:0043627 response to estrogen
GO:0046449 creatinine metabolic process
GO:0050435 amyloid-beta metabolic process
GO:0050769 positive regulation of neurogenesis
GO:0061837 neuropeptide processing
GO:0071345 cellular response to cytokine stimulus
GO:0071492 cellular response to UV-A
GO:0071493 cellular response to UV-B
GO:0090399 replicative senescence
GO:0097242 amyloid-beta clearance
GO:0150094 amyloid-beta clearance by cellular catabolic process
GO:1900273 positive regulation of long-term synaptic potentiation
Cellular Component
GO:0005737 cytoplasm
GO:0005769 early endosome
GO:0005802 trans-Golgi network
GO:0005886 plasma membrane
GO:0005903 brush border
GO:0005925 focal adhesion
GO:0008021 synaptic vesicle
GO:0009986 cell surface
GO:0016020 membrane
GO:0030424 axon
GO:0030425 dendrite
GO:0030667 secretory granule membrane
GO:0031410 cytoplasmic vesicle
GO:0043025 neuronal cell body
GO:0044306 neuron projection terminus
GO:0045121 membrane raft
GO:0045202 synapse
GO:0070062 extracellular exosome
GO:0098793 presynapse

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Molecular Function
View graph for
Biological Process
View graph for
Cellular Component
External links
PDB RCSB:1r1i, PDBe:1r1i, PDBj:1r1i
PDBsum1r1i
PubMed14747736
UniProtP08473|NEP_HUMAN Neprilysin (Gene Name=MME)

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