Binding Site Information of Target
| Target General Information | Top | ||||
|---|---|---|---|---|---|
| Target ID | T05409 | Target Info | |||
| Target Name | Neutral endopeptidase (MME) | ||||
| Synonyms | Skin fibroblast elastase; SFE; Neutral endopeptidase 24.11; Neprilysin; NEP protein; Enkephalinase; EPN; Common acute lymphocytic leukemia antigen; CD10; CALLA; Atriopeptidase | ||||
| Target Type | Clinical trial Target | ||||
| Gene Name | MME | ||||
| Biochemical Class | Peptidase | ||||
| UniProt ID | |||||
| Drug Binding Sites of Target | Top | |||||
|---|---|---|---|---|---|---|
| Ligand Name: Sampatrilat | Ligand Info | |||||
| Structure Description | Crystal structure of Neprilysin in complex with Sampatrilat. | PDB:6XVP | ||||
| Method | X-ray diffraction | Resolution | 2.65 Å | Mutation | No | [1] |
| PDB Sequence |
GICKSSDCIK
63 SAARLIQNMD73 ATTEPCTDFF83 KYACGGWLKR93 NVIPETSSRY103 GNFDILRDEL 113 EVVLKDVLQE123 PKTEDIVAVQ133 KAKALYRSCI143 NESAIDSRGG153 EPLLKLLPDI 163 YGWPVATENW173 EQKYGASWTA183 EKAIAQLNSK193 YGKKVLINLF203 VGTDDKNSVN 213 HVIHIDQPRL223 GLPSRDYYEC233 TGIYKEACTA243 YVDFMISVAR253 LIRQEERLPI 263 DENQLALEMN273 KVMELEKEIA283 NATAKPEDRN293 DPMLLYNKMT303 LAQIQNNFSL 313 EINGKPFSWL323 NFTNEIMSTV333 NISITNEEDV343 VVYAPEYLTK353 LKPILTKYSA 363 RDLQNLMSWR373 FIMDLVSSLS383 RTYKESRNAF393 RKALYGTTSE403 TATWRRCANY 413 VNGNMENAVG423 RLYVEAAFAG433 ESKHVVEDLI443 AQIREVFIQT453 LDDLTWMDAE 463 TKKRAEEKAL473 AIKERIGYPD483 DIVSNDNKLN493 NEYLELNYKE503 DEYFENIIQN 513 LKFSQSKQLK523 KLREKVDKDE533 WISGAAVVNA543 FYSSGRNQIV553 FPAGILQPPF 563 FSAQQSNSLN573 YGGIGMVIGH583 EITHGFDDNG593 RNFNKDGDLV603 DWWTQQSASN 613 FKEQSQCMVY623 QYGNFSWDLA633 GGQHLNGINT643 LGENIADNGG653 LGQAYRAYQN 663 YIKKNGEEKL673 LPGLDLNHKQ683 LFFLNFAQVW693 CGTYRPEYAV703 NSIKTDVHSP 713 GNFRIIGTLQ723 NSAEFSEAFH733 CRKNSYMNPE743 KKCRVW
|
|||||
|
|
ARG102
2.293
TYR103
4.830
GLY104
4.777
PHE106
3.044
ASP107
2.897
ARG110
3.045
ILE535
4.358
ASN542
2.189
ALA543
2.856
PHE544
3.066
TYR545
3.509
SER546
4.914
ILE558
4.209
PHE563
4.714
|
|||||
| Ligand Name: Omapatrilat | Ligand Info | |||||
| Structure Description | Crystal structure of Neprilysin in complex with Omapatrilat. | PDB:6SUK | ||||
| Method | X-ray diffraction | Resolution | 1.75 Å | Mutation | No | [1] |
| PDB Sequence |
DDGICKSSDC
61 IKSAARLIQN71 MDATTEPCTD81 FFKYACGGWL91 KRNVIPETSS101 RYGNFDILRD 111 ELEVVLKDVL121 QEPKTEDIVA131 VQKAKALYRS141 CINESAIDSR151 GGEPLLKLLP 161 DIYGWPVATE171 NWEQKYGASW181 TAEKAIAQLN191 SKYGKKVLIN201 LFVGTDDKNS 211 VNHVIHIDQP221 RLGLPSRDYY231 ECTGIYKEAC241 TAYVDFMISV251 ARLIRQEERL 261 PIDENQLALE271 MNKVMELEKE281 IANATAKPED291 RNDPMLLYNK301 MTLAQIQNNF 311 SLEINGKPFS321 WLNFTNEIMS331 TVNISITNEE341 DVVVYAPEYL351 TKLKPILTKY 361 SARDLQNLMS371 WRFIMDLVSS381 LSRTYKESRN391 AFRKALYGTT401 SETATWRRCA 411 NYVNGNMENA421 VGRLYVEAAF431 AGESKHVVED441 LIAQIREVFI451 QTLDDLTWMD 461 AETKKRAEEK471 ALAIKERIGY481 PDDIVSNDNK491 LNNEYLELNY501 KEDEYFENII 511 QNLKFSQSKQ521 LKKLREKVDK531 DEWISGAAVV541 NAFYSSGRNQ551 IVFPAGILQP 561 PFFSAQQSNS571 LNYGGIGMVI581 GHEITHGFDD591 NGRNFNKDGD601 LVDWWTQQSA 611 SNFKEQSQCM621 VYQYGNFSWD631 LAGGQHLNGI641 NTLGENIADN651 GGLGQAYRAY 661 QNYIKKNGEE671 KLLPGLDLNH681 KQLFFLNFAQ691 VWCGTYRPEY701 AVNSIKTDVH 711 SPGNFRIIGT721 LQNSAEFSEA731 FHCRKNSYMN741 PEKKCRVW
|
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|
|
ARG102
2.321
PHE106
1.872
ARG110
2.259
VAL541
4.402
ASN542
2.152
ALA543
2.659
PHE544
4.229
ILE558
2.741
PHE563
2.746
MET579
2.638
VAL580
2.656
HIS583
2.406
|
|||||
| Ligand Name: LBQ657 | Ligand Info | |||||
| Structure Description | NEPRILYSIN COMPLEXED WITH LBQ657 | PDB:5JMY | ||||
| Method | X-ray diffraction | Resolution | 2.00 Å | Mutation | No | [2] |
| PDB Sequence |
GICKSSDCIK
63 SAARLIQNMD73 ATTEPCTDFF83 KYACGGWLKR93 NVIPETSSRY103 GNFDILRDEL 113 EVVLKDVLQE123 PKTEDIVAVQ133 KAKALYRSCI143 NESAIDSRGG153 EPLLKLLPDI 163 YGWPVATENW173 EQKYGASWTA183 EKAIAQLNSK193 YGKKVLINLF203 VGTDDKNSVN 213 HVIHIDQPRL223 GLPSRDYYEC233 TGIYKEACTA243 YVDFMISVAR253 LIRQEERLPI 263 DENQLALEMN273 KVMELEKEIA283 NATAKPEDRN293 DPMLLYNKMT303 LAQIQNNFSL 313 EINGKPFSWL323 NFTNEIMSTV333 NISITNEEDV343 VVYAPEYLTK353 LKPILTKYSA 363 RDLQNLMSWR373 FIMDLVSSLS383 RTYKESRNAF393 RKALYGTTSE403 TATWRRCANY 413 VNGNMENAVG423 RLYVEAAFAG433 ESKHVVEDLI443 AQIREVFIQT453 LDDLTWMDAE 463 TKKRAEEKAL473 AIKERIGYPD483 DIVSNDNKLN493 NEYLELNYKE503 DEYFENIIQN 513 LKFSQSKQLK523 KLREKVDKDE533 WISGAAVVNA543 FYSSGRNQIV553 FPAGILQPPF 563 FSAQQSNSLN573 YGGIGMVIGH583 EITHGFDDNG593 RNFNKDGDLV603 DWWTQQSASN 613 FKEQSQCMVY623 QYGNFSWDLA633 GGQHLNGINT643 LGENIADNGG653 LGQAYRAYQN 663 YIKKNGEEKL673 LPGLDLNHKQ683 LFFLNFAQVW693 CGTYRPEYAV703 NSIKTDVHSP 713 GNFRIIGTLQ723 NSAEFSEAFH733 CRKNSYMNPE743 KKCRVW
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Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .6LD or .6LD2 or .6LD3 or :36LD;style chemicals stick;color identity;select .A:102 or .A:106 or .A:110 or .A:542 or .A:543 or .A:544 or .A:558 or .A:563 or .A:575 or .A:579 or .A:580 or .A:583 or .A:584 or .A:587 or .A:646 or .A:650 or .A:689 or .A:692 or .A:693 or .A:709 or .A:711 or .A:717 or .A:718; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
ARG102
3.048
PHE106
3.499
ARG110
2.919
ASN542
2.881
ALA543
3.020
PHE544
3.690
ILE558
4.409
PHE563
3.999
GLY575
4.949
MET579
3.564
VAL580
3.795
HIS583
3.483
|
|||||
| Ligand Name: Phosphoramidon | Ligand Info | |||||
| Structure Description | STRUCTURE OF HUMAN NEUTRAL ENDOPEPTIDASE COMPLEXED WITH PHOSPHORAMIDON | PDB:1DMT | ||||
| Method | X-ray diffraction | Resolution | 2.10 Å | Mutation | No | [3] |
| PDB Sequence |
GICKSSDCIK
63 SAARLIQNMD73 ATTEPCTDFF83 KYACGGWLKR93 NVIPETSSRY103 GNFDILRDEL 113 EVVLKDVLQE123 PKTEDIVAVQ133 KAKALYRSCI143 NESAIDSRGG153 EPLLKLLPDI 163 YGWPVATENW173 EQKYGASWTA183 EKAIAQLNSK193 YGKKVLINLF203 VGTDDKNSVN 213 HVIHIDQPRL223 GLPSRDYYEC233 TGIYKEACTA243 YVDFMISVAR253 LIRQEERLPI 263 DENQLALEMN273 KVMELEKEIA283 NATAKPEDRN293 DPMLLYNKMT303 LAQIQNNFSL 313 EINGKPFSWL323 NFTNEIMSTV333 NISITNEEDV343 VVYAPEYLTK353 LKPILTKYSA 363 RDLQNLMSWR373 FIMDLVSSLS383 RTYKESRNAF393 RKALYGTTSE403 TATWRRCANY 413 VNGNMENAVG423 RLYVEAAFAG433 ESKHVVEDLI443 AQIREVFIQT453 LDDLTWMDAE 463 TKKRAEEKAL473 AIKERIGYPD483 DIVSNDNKLN493 NEYLELNYKE503 DEYFENIIQN 513 LKFSQSKQLK523 KLREKVDKDE533 WISGAAVVNA543 FYSSGRNQIV553 FPAGILQPPF 563 FSAQQSNSLN573 YGGIGMVIGH583 EITHGFDDNG593 RNFNKDGDLV603 DWWTQQSASN 613 FKEQSQCMVY623 QYGNFSWDLA633 GGQHLNGINT643 LGENIADNGG653 LGQAYRAYQN 663 YIKKNGEEKL673 LPGLDLNHKQ683 LFFLNFAQVW693 CGTYRPEYAV703 NSIKTDVHSP 713 GNFRIIGTLQ723 NSAEFSEAFH733 CRKNSYMNPE743 KKCRVW
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|
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .RDF or .RDF2 or .RDF3 or :3RDF;style chemicals stick;color identity;select .A:102 or .A:106 or .A:107 or .A:110 or .A:541 or .A:542 or .A:543 or .A:544 or .A:545 or .A:558 or .A:563 or .A:579 or .A:580 or .A:583 or .A:584 or .A:587 or .A:646 or .A:693 or .A:709 or .A:710 or .A:711 or .A:717; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
ARG102
3.594
PHE106
3.387
ASP107
4.119
ARG110
3.487
VAL541
2.835
ASN542
3.112
ALA543
2.894
PHE544
3.530
TYR545
4.431
ILE558
3.301
PHE563
4.107
|
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| Click to View More Binding Site Information of This Target and Ligand Pair | ||||||
| Ligand Name: [2(R,S)-2-Sulfanylheptanoyl]-Phe-Ala | Ligand Info | |||||
| Structure Description | STRUCTURAL ANALYSIS OF NEPRILYSIN WITH VARIOUS SPECIFIC AND POTENT INHIBITORS | PDB:1R1I | ||||
| Method | X-ray diffraction | Resolution | 2.60 Å | Mutation | No | [4] |
| PDB Sequence |
GICKSSDCIK
63 SAARLIQNMD73 ATTEPCTDFF83 KYACGGWLKR93 NVIPETSSRY103 GNFDILRDEL 113 EVVLKDVLQE123 PKTEDIVAVQ133 KAKALYRSCI143 NESAIDSRGG153 EPLLKLLPDI 163 YGWPVATENW173 EQKYGASWTA183 EKAIAQLNSK193 YGKKVLINLF203 VGTDDKNSVN 213 HVIHIDQPRL223 GLPSRDYYEC233 TGIYKEACTA243 YVDFMISVAR253 LIRQEERLPI 263 DENQLALEMN273 KVMELEKEIA283 NATAKPEDRN293 DPMLLYNKMT303 LAQIQNNFSL 313 EINGKPFSWL323 NFTNEIMSTV333 NISITNEEDV343 VVYAPEYLTK353 LKPILTKYSA 363 RDLQNLMSWR373 FIMDLVSSLS383 RTYKESRNAF393 RKALYGTTSE403 TATWRRCANY 413 VNGNMENAVG423 RLYVEAAFAG433 ESKHVVEDLI443 AQIREVFIQT453 LDDLTWMDAE 463 TKKRAEEKAL473 AIKERIGYPD483 DIVSNDNKLN493 NEYLELNYKE503 DEYFENIIQN 513 LKFSQSKQLK523 KLREKVDKDE533 WISGAAVVNA543 FYSSGRNQIV553 FPAGILQPPF 563 FSAQQSNSLN573 YGGIGMVIGH583 EITHGFDDNG593 RNFNKDGDLV603 DWWTQQSASN 613 FKEQSQCMVY623 QYGNFSWDLA633 GGQHLNGINT643 LGENIADNGG653 LGQAYRAYQN 663 YIKKNGEEKL673 LPGLDLNHKQ683 LFFLNFAQVW693 CGTYRPEYAV703 NSIKTDVHSP 713 GNFRIIGTLQ723 NSAEFSEAFH733 CRKNSYMNPE743 KKCRVW
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|
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .TI1 or .TI12 or .TI13 or :3TI1;style chemicals stick;color identity;select .A:102 or .A:106 or .A:110 or .A:542 or .A:543 or .A:544 or .A:545 or .A:558 or .A:563 or .A:579 or .A:580 or .A:583 or .A:584 or .A:587 or .A:646 or .A:650 or .A:692 or .A:693 or .A:709 or .A:710 or .A:711 or .A:717; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
ARG102
4.743
PHE106
3.497
ARG110
3.819
ASN542
2.770
ALA543
3.390
PHE544
3.848
TYR545
4.712
ILE558
4.518
PHE563
3.951
MET579
3.277
VAL580
2.873
|
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| Ligand Name: Sampatrilat-Asp | Ligand Info | |||||
| Structure Description | Crystal structure of Neprilysin in complex with Sampatrilat-ASP. | PDB:6SVY | ||||
| Method | X-ray diffraction | Resolution | 2.60 Å | Mutation | No | [1] |
| PDB Sequence |
DGICKSSDCI
62 KSAARLIQNM72 DATTEPCTDF82 FKYACGGWLK92 RNVIPETSSR102 YGNFDILRDE 112 LEVVLKDVLQ122 EPKTEDIVAV132 QKAKALYRSC142 INESAIDSRG152 GEPLLKLLPD 162 IYGWPVATEN172 WEQKYGASWT182 AEKAIAQLNS192 KYGKKVLINL202 FVGTDDKNSV 212 NHVIHIDQPR222 LGLPSRDYYE232 CTGIYKEACT242 AYVDFMISVA252 RLIRQEERLP 262 IDENQLALEM272 NKVMELEKEI282 ANATAKPEDR292 NDPMLLYNKM302 TLAQIQNNFS 312 LEINGKPFSW322 LNFTNEIMST332 VNISITNEED342 VVVYAPEYLT352 KLKPILTKYS 362 ARDLQNLMSW372 RFIMDLVSSL382 SRTYKESRNA392 FRKALYGTTS402 ETATWRRCAN 412 YVNGNMENAV422 GRLYVEAAFA432 GESKHVVEDL442 IAQIREVFIQ452 TLDDLTWMDA 462 ETKKRAEEKA472 LAIKERIGYP482 DDIVSNDNKL492 NNEYLELNYK502 EDEYFENIIQ 512 NLKFSQSKQL522 KKLREKVDKD532 EWISGAAVVN542 AFYSSGRNQI552 VFPAGILQPP 562 FFSAQQSNSL572 NYGGIGMVIG582 HEITHGFDDN592 GRNFNKDGDL602 VDWWTQQSAS 612 NFKEQSQCMV622 YQYGNFSWDL632 AGGQHLNGIN642 TLGENIADNG652 GLGQAYRAYQ 662 NYIKKNGEEK672 LLPGLDLNHK682 QLFFLNFAQV692 WCGTYRPEYA702 VNSIKTDVHS 712 PGNFRIIGTL722 QNSAEFSEAF732 HCRKNSYMNP742 EKKCRVW
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|
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .D0W or .D0W2 or .D0W3 or :3D0W;style chemicals stick;color identity;select .A:102 or .A:103 or .A:104 or .A:106 or .A:107 or .A:110 or .A:541 or .A:542 or .A:543 or .A:544 or .A:545 or .A:558 or .A:563 or .A:579 or .A:580 or .A:583 or .A:584 or .A:587 or .A:646 or .A:650 or .A:692 or .A:693 or .A:695 or .A:697 or .A:709 or .A:710 or .A:711 or .A:714 or .A:717; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
ARG102
2.221
TYR103
4.696
GLY104
3.999
PHE106
2.596
ASP107
2.514
ARG110
2.102
VAL541
4.802
ASN542
2.045
ALA543
2.385
PHE544
2.621
TYR545
3.435
ILE558
3.732
PHE563
4.057
MET579
4.008
VAL580
2.395
|
|||||
| Ligand Name: N-[3-[(1-Aminoethyl)(hydroxy)phosphoryl]-2-(1,1'-biphenyl-4-ylmethyl)propanoyl]alanine | Ligand Info | |||||
| Structure Description | STRUCTURAL ANALYSIS OF NEPRILYSIN WITH VARIOUS SPECIFIC AND POTENT INHIBITORS | PDB:1R1H | ||||
| Method | X-ray diffraction | Resolution | 1.95 Å | Mutation | No | [4] |
| PDB Sequence |
GICKSSDCIK
63 SAARLIQNMD73 ATTEPCTDFF83 KYACGGWLKR93 NVIPETSSRY103 GNFDILRDEL 113 EVVLKDVLQE123 PKTEDIVAVQ133 KAKALYRSCI143 NESAIDSRGG153 EPLLKLLPDI 163 YGWPVATENW173 EQKYGASWTA183 EKAIAQLNSK193 YGKKVLINLF203 VGTDDKNSVN 213 HVIHIDQPRL223 GLPSRDYYEC233 TGIYKEACTA243 YVDFMISVAR253 LIRQEERLPI 263 DENQLALEMN273 KVMELEKEIA283 NATAKPEDRN293 DPMLLYNKMT303 LAQIQNNFSL 313 EINGKPFSWL323 NFTNEIMSTV333 NISITNEEDV343 VVYAPEYLTK353 LKPILTKYSA 363 RDLQNLMSWR373 FIMDLVSSLS383 RTYKESRNAF393 RKALYGTTSE403 TATWRRCANY 413 VNGNMENAVG423 RLYVEAAFAG433 ESKHVVEDLI443 AQIREVFIQT453 LDDLTWMDAE 463 TKKRAEEKAL473 AIKERIGYPD483 DIVSNDNKLN493 NEYLELNYKE503 DEYFENIIQN 513 LKFSQSKQLK523 KLREKVDKDE533 WISGAAVVNA543 FYSSGRNQIV553 FPAGILQPPF 563 FSAQQSNSLN573 YGGIGMVIGH583 EITHGFDDNG593 RNFNKDGDLV603 DWWTQQSASN 613 FKEQSQCMVY623 QYGNFSWDLA633 GGQHLNGINT643 LGENIADNGG653 LGQAYRAYQN 663 YIKKNGEEKL673 LPGLDLNHKQ683 LFFLNFAQVW693 CGTYRPEYAV703 NSIKTDVHSP 713 GNFRIIGTLQ723 NSAEFSEAFH733 CRKNSYMNPE743 KKCRVW
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|
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .BIR or .BIR2 or .BIR3 or :3BIR;style chemicals stick;color identity;select .A:102 or .A:106 or .A:110 or .A:542 or .A:543 or .A:544 or .A:545 or .A:558 or .A:563 or .A:575 or .A:576 or .A:579 or .A:580 or .A:583 or .A:584 or .A:587 or .A:646 or .A:650 or .A:689 or .A:692 or .A:693 or .A:709 or .A:711 or .A:717; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
ARG102
4.823
PHE106
3.652
ARG110
4.395
ASN542
2.973
ALA543
2.731
PHE544
3.397
TYR545
4.182
ILE558
4.609
PHE563
3.930
GLY575
4.628
GLY576
4.973
MET579
3.834
|
|||||
| Ligand Name: (2s)-2-({(2s)-3-[(R)-[(1r)-1-({(4s)-4-Amino-5-[(2s)-2-Cyanopyrrolidin-1-Yl]-5-Oxopentanoyl}amino)ethyl](Hydroxy)phosphoryl]-2-Benzylpropanoyl}amino)propanoic Acid | Ligand Info | |||||
| Structure Description | Human NEP complexed with a bifunctional NEP/DPP IV inhibitor | PDB:2QPJ | ||||
| Method | X-ray diffraction | Resolution | 2.05 Å | Mutation | No | [5] |
| PDB Sequence |
GICKSSDCIK
63 SAARLIQNMD73 ATTEPCTDFF83 KYACGGWLKR93 NVIPETSSRY103 GNFDILRDEL 113 EVVLKDVLQE123 PKTEDIVAVQ133 KAKALYRSCI143 NESAIDSRGG153 EPLLKLLPDI 163 YGWPVATENW173 EQKYGASWTA183 EKAIAQLNSK193 YGKKVLINLF203 VGTDDKNSVN 213 HVIHIDQPRL223 GLPSRDYYEC233 TGIYKEACTA243 YVDFMISVAR253 LIRQEERLPI 263 DENQLALEMN273 KVMELEKEIA283 NATAKPEDRN293 DPMLLYNKMT303 LAQIQNNFSL 313 EINGKPFSWL323 NFTNEIMSTV333 NISITNEEDV343 VVYAPEYLTK353 LKPILTKYSA 363 RDLQNLMSWR373 FIMDLVSSLS383 RTYKESRNAF393 RKALYGTTSE403 TATWRRCANY 413 VNGNMENAVG423 RLYVEAAFAG433 ESKHVVEDLI443 AQIREVFIQT453 LDDLTWMDAE 463 TKKRAEEKAL473 AIKERIGYPD483 DIVSNDNKLN493 NEYLELNYKE503 DEYFENIIQN 513 LKFSQSKQLK523 KLREKVDKDE533 WISGAAVVNA543 FYSSGRNQIV553 FPAGILQPPF 563 FSAQQSNSLN573 YGGIGMVIGH583 EITHGFDDNG593 RNFNKDGDLV603 DWWTQQSASN 613 FKEQSQCMVY623 QYGNFSWDLA633 GGQHLNGINT643 LGENIADNGG653 LGQAYRAYQN 663 YIKKNGEEKL673 LPGLDLNHKQ683 LFFLNFAQVW693 CGTYRPEYAV703 NSIKTDVHSP 713 GNFRIIGTLQ723 NSAEFSEAFH733 CRKNSYMNPE743 KKCRVW
|
|||||
|
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .I20 or .I202 or .I203 or :3I20;style chemicals stick;color identity;select .A:102 or .A:106 or .A:110 or .A:542 or .A:543 or .A:544 or .A:545 or .A:546 or .A:547 or .A:548 or .A:558 or .A:563 or .A:579 or .A:580 or .A:583 or .A:584 or .A:587 or .A:592 or .A:646 or .A:650 or .A:692 or .A:693 or .A:709 or .A:711 or .A:717; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
ARG102
4.910
PHE106
3.237
ARG110
4.410
ASN542
2.923
ALA543
3.030
PHE544
3.226
TYR545
1.959
SER546
3.914
SER547
2.703
GLY548
4.399
ILE558
4.736
PHE563
4.110
MET579
3.692
|
|||||
| Ligand Name: 2-[(1S)-1-Benzyl-2-sulfanylethyl]-1H-imidazo[4,5-C]pyridin-5-ium | Ligand Info | |||||
| Structure Description | Crystal Structure of human NEP complexed with an imidazo[4,5-c]pyridine inhibitor | PDB:1Y8J | ||||
| Method | X-ray diffraction | Resolution | 2.25 Å | Mutation | No | [6] |
| PDB Sequence |
GICKSSDCIK
63 SAARLIQNMD73 ATTEPCTDFF83 KYACGGWLKR93 NVIPETSSRY103 GNFDILRDEL 113 EVVLKDVLQE123 PKTEDIVAVQ133 KAKALYRSCI143 NESAIDSRGG153 EPLLKLLPDI 163 YGWPVATENW173 EQKYGASWTA183 EKAIAQLNSK193 YGKKVLINLF203 VGTDDKNSVN 213 HVIHIDQPRL223 GLPSRDYYEC233 TGIYKEACTA243 YVDFMISVAR253 LIRQEERLPI 263 DENQLALEMN273 KVMELEKEIA283 NATAKPEDRN293 DPMLLYNKMT303 LAQIQNNFSL 313 EINGKPFSWL323 NFTNEIMSTV333 NISITNEEDV343 VVYAPEYLTK353 LKPILTKYSA 363 RDLQNLMSWR373 FIMDLVSSLS383 RTYKESRNAF393 RKALYGTTSE403 TATWRRCANY 413 VNGNMENAVG423 RLYVEAAFAG433 ESKHVVEDLI443 AQIREVFIQT453 LDDLTWMDAE 463 TKKRAEEKAL473 AIKERIGYPD483 DIVSNDNKLN493 NEYLELNYKE503 DEYFENIIQN 513 LKFSQSKQLK523 KLREKVDKDE533 WISGAAVVNA543 FYSSGRNQIV553 FPAGILQPPF 563 FSAQQSNSLN573 YGGIGMVIGH583 EITHGFDDNG593 RNFNKDGDLV603 DWWTQQSASN 613 FKEQSQCMVY623 QYGNFSWDLA633 GGQHLNGINT643 LGENIADNGG653 LGQAYRAYQN 663 YIKKNGEEKL673 LPGLDLNHKQ683 LFFLNFAQVW693 CGTYRPEYAV703 NSIKTDVHSP 713 GNFRIIGTLQ723 NSAEFSEAFH733 CRKNSYMNPE743 KKCRVW
|
|||||
|
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .STS or .STS2 or .STS3 or :3STS;style chemicals stick;color identity;select .A:102 or .A:106 or .A:110 or .A:542 or .A:543 or .A:558 or .A:563 or .A:579 or .A:580 or .A:583 or .A:584 or .A:587 or .A:646 or .A:650 or .A:692 or .A:693 or .A:709 or .A:711 or .A:717; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
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| Ligand Name: N-(3-Phenyl-2-sulfanylpropanoyl)phenylalanylalanine | Ligand Info | |||||
| Structure Description | STRUCTURAL ANALYSIS OF NEPRILYSIN WITH VARIOUS SPECIFIC AND POTENT INHIBITORS | PDB:1R1J | ||||
| Method | X-ray diffraction | Resolution | 2.35 Å | Mutation | No | [4] |
| PDB Sequence |
GICKSSDCIK
63 SAARLIQNMD73 ATTEPCTDFF83 KYACGGWLKR93 NVIPETSSRY103 GNFDILRDEL 113 EVVLKDVLQE123 PKTEDIVAVQ133 KAKALYRSCI143 NESAIDSRGG153 EPLLKLLPDI 163 YGWPVATENW173 EQKYGASWTA183 EKAIAQLNSK193 YGKKVLINLF203 VGTDDKNSVN 213 HVIHIDQPRL223 GLPSRDYYEC233 TGIYKEACTA243 YVDFMISVAR253 LIRQEERLPI 263 DENQLALEMN273 KVMELEKEIA283 NATAKPEDRN293 DPMLLYNKMT303 LAQIQNNFSL 313 EINGKPFSWL323 NFTNEIMSTV333 NISITNEEDV343 VVYAPEYLTK353 LKPILTKYSA 363 RDLQNLMSWR373 FIMDLVSSLS383 RTYKESRNAF393 RKALYGTTSE403 TATWRRCANY 413 VNGNMENAVG423 RLYVEAAFAG433 ESKHVVEDLI443 AQIREVFIQT453 LDDLTWMDAE 463 TKKRAEEKAL473 AIKERIGYPD483 DIVSNDNKLN493 NEYLELNYKE503 DEYFENIIQN 513 LKFSQSKQLK523 KLREKVDKDE533 WISGAAVVNA543 FYSSGRNQIV553 FPAGILQPPF 563 FSAQQSNSLN573 YGGIGMVIGH583 EITHGFDDNG593 RNFNKDGDLV603 DWWTQQSASN 613 FKEQSQCMVY623 QYGNFSWDLA633 GGQHLNGINT643 LGENIADNGG653 LGQAYRAYQN 663 YIKKNGEEKL673 LPGLDLNHKQ683 LFFLNFAQVW693 CGTYRPEYAV703 NSIKTDVHSP 713 GNFRIIGTLQ723 NSAEFSEAFH733 CRKNSYMNPE743 KKCRVW
|
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|
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .OIR or .OIR2 or .OIR3 or :3OIR;style chemicals stick;color identity;select .A:102 or .A:106 or .A:110 or .A:542 or .A:543 or .A:544 or .A:545 or .A:558 or .A:563 or .A:579 or .A:580 or .A:583 or .A:584 or .A:587 or .A:646 or .A:650 or .A:692 or .A:693 or .A:709 or .A:710 or .A:711 or .A:717; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
ARG102
4.455
PHE106
3.479
ARG110
3.789
ASN542
3.263
ALA543
3.328
PHE544
3.397
TYR545
4.142
ILE558
4.276
PHE563
3.738
MET579
2.569
VAL580
3.570
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| Ligand Name: Heteroarylalanine 5-Phenyl Oxazole | Ligand Info | |||||
| Structure Description | Crystal Structure of Human Neutral Endopeptidase complexed with a heteroarylalanine diacid. | PDB:2YB9 | ||||
| Method | X-ray diffraction | Resolution | 2.40 Å | Mutation | No | [7] |
| PDB Sequence |
GICKSSDCIK
63 SAARLIQNMD73 ATTEPCTDFF83 KYACGGWLKR93 NVIPETSSRY103 GNFDILRDEL 113 EVVLKDVLQE123 PKTEDIVAVQ133 KAKALYRSCI143 NESAIDSRGG153 EPLLKLLPDI 163 YGWPVATENW173 EQKYGASWTA183 EKAIAQLNSK193 YGKKVLINLF203 VGTDDKNSVN 213 HVIHIDQPRL223 GLPSRDYYEC233 TGIYKEACTA243 YVDFMISVAR253 LIRQEERLPI 263 DENQLALEMN273 KVMELEKEIA283 NATAKPEDRN293 DPMLLYNKMT303 LAQIQNNFSL 313 EINGKPFSWL323 NFTNEIMSTV333 NISITNEEDV343 VVYAPEYLTK353 LKPILTKYSA 363 RDLQNLMSWR373 FIMDLVSSLS383 RTYKESRNAF393 RKALYGTTSE403 TATWRRCANY 413 VNGNMENAVG423 RLYVEAAFAG433 ESKHVVEDLI443 AQIREVFIQT453 LDDLTWMDAE 463 TKKRAEEKAL473 AIKERIGYPD483 DIVSNDNKLN493 NEYLELNYKE503 DEYFENIIQN 513 LKFSQSKQLK523 KLREKVDKDE533 WISGAAVVNA543 FYSSGRNQIV553 FPAGILQPPF 563 FSAQQSNSLN573 YGGIGMVIGH583 EITHGFDDNG593 RNFNKDGDLV603 DWWTQQSASN 613 FKEQSQCMVY623 QYGNFSWDLA633 GGQHLNGINT643 LGENIADNGG653 LGQAYRAYQN 663 YIKKNGEEKL673 LPGLDLNHKQ683 LFFLNFAQVW693 CGTYRPEYAV703 NSIKTDVHSP 713 GNFRIIGTLQ723 NSAEFSEAFH733 CRKNSYMNPE743 KKCRVW
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|
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .HA0 or .HA02 or .HA03 or :3HA0;style chemicals stick;color identity;select .A:102 or .A:103 or .A:104 or .A:106 or .A:107 or .A:110 or .A:542 or .A:543 or .A:544 or .A:558 or .A:579 or .A:580 or .A:583 or .A:584 or .A:587 or .A:646 or .A:693 or .A:694 or .A:695 or .A:696 or .A:697 or .A:709 or .A:711 or .A:714 or .A:717; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
ARG102
3.140
TYR103
3.715
GLY104
4.849
PHE106
3.437
ASP107
3.510
ARG110
3.118
ASN542
2.743
ALA543
3.170
PHE544
3.792
ILE558
4.294
MET579
4.911
VAL580
3.918
HIS583
3.365
|
|||||
| Ligand Name: (R)-4-(1-carboxy-3-(3'-chlorobiphenyl-4-yl)propan-2-ylamino)-4-oxobutanoic acid | Ligand Info | |||||
| Structure Description | Neprilysin in complex with the inhibitor (R)-4-(1-carboxy-3-(3'-chlorobiphenyl-4-yl)propan-2-ylamino)-4-oxobutanoic acid | PDB:6THP | ||||
| Method | X-ray diffraction | Resolution | 2.54 Å | Mutation | No | [8] |
| PDB Sequence |
GICKSSDCIK
63 SAARLIQNMD73 ATTEPCTDFF83 KYACGGWLKR93 NVIPETSSRY103 GNFDILRDEL 113 EVVLKDVLQE123 PKTEDIVAVQ133 KAKALYRSCI143 NESAIDSRGG153 EPLLKLLPDI 163 YGWPVATENW173 EQKYGASWTA183 EKAIAQLNSK193 YGKKVLINLF203 VGTDDKNSVN 213 HVIHIDQPRL223 GLPSRDYYEC233 TGIYKEACTA243 YVDFMISVAR253 LIRQEERLPI 263 DENQLALEMN273 KVMELEKEIA283 NATAKPEDRN293 DPMLLYNKMT303 LAQIQNNFSL 313 EINGKPFSWL323 NFTNEIMSTV333 NISITNEEDV343 VVYAPEYLTK353 LKPILTKYSA 363 RDLQNLMSWR373 FIMDLVSSLS383 RTYKESRNAF393 RKALYGTTSE403 TATWRRCANY 413 VNGNMENAVG423 RLYVEAAFAG433 ESKHVVEDLI443 AQIREVFIQT453 LDDLTWMDAE 463 TKKRAEEKAL473 AIKERIGYPD483 DIVSNDNKLN493 NEYLELNYKE503 DEYFENIIQN 513 LKFSQSKQLK523 KLREKVDKDE533 WISGAAVVNA543 FYSSGRNQIV553 FPAGILQPPF 563 FSAQQSNSLN573 YGGIGMVIGH583 EITHGFDDNG593 RNFNKDGDLV603 DWWTQQSASN 613 FKEQSQCMVY623 QYGNFSWDLA633 GGQHLNGINT643 LGENIADNGG653 LGQAYRAYQN 663 YIKKNGEEKL673 LPGLDLNHKQ683 LFFLNFAQVW693 CGTYRPEYAV703 NSIKTDVHSP 713 GNFRIIGTLQ723 NSAEFSEAFH733 CRKNSYMNPE743 KKCRVW
|
|||||
|
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .N9Q or .N9Q2 or .N9Q3 or :3N9Q;style chemicals stick;color identity;select .A:102 or .A:106 or .A:110 or .A:542 or .A:543 or .A:544 or .A:558 or .A:563 or .A:575 or .A:579 or .A:580 or .A:583 or .A:584 or .A:587 or .A:646 or .A:650 or .A:689 or .A:692 or .A:693 or .A:709 or .A:711 or .A:717 or .A:718 or .A:721; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
ARG102
3.078
PHE106
3.858
ARG110
3.228
ASN542
2.867
ALA543
3.243
PHE544
4.873
ILE558
4.754
PHE563
4.272
GLY575
4.806
MET579
3.002
VAL580
3.602
HIS583
3.233
|
|||||
| References | Top | ||||
|---|---|---|---|---|---|
| REF 1 | Molecular Basis for Omapatrilat and Sampatrilat Binding to Neprilysin-Implications for Dual Inhibitor Design with Angiotensin-Converting Enzyme. J Med Chem. 2020 May 28;63(10):5488-5500. | ||||
| REF 2 | Structure of neprilysin in complex with the active metabolite of sacubitril. Sci Rep. 2016 Jun 15;6:27909. | ||||
| REF 3 | Structure of human neutral endopeptidase (Neprilysin) complexed with phosphoramidon. J Mol Biol. 2000 Feb 18;296(2):341-9. | ||||
| REF 4 | Structural analysis of neprilysin with various specific and potent inhibitors. Acta Crystallogr D Biol Crystallogr. 2004 Feb;60(Pt 2):392-6. | ||||
| REF 5 | Structural studies of a bifunctional inhibitor of neprilysin and DPP-IV. Acta Crystallogr D Biol Crystallogr. 2007 Sep;63(Pt 9):975-81. | ||||
| REF 6 | Second-Generation Inhibitors for the Metalloprotease Neprilysin Based on Bicyclic Heteroaromatic Scaffolds: Synthesis, Biological Activity, and X-ray Crystal Structure Analysis. doi:10.1002/hlca.200590051. | ||||
| REF 7 | Synthesis and evaluation of heteroarylalanine diacids as potent and selective neutral endopeptidase inhibitors. Bioorg Med Chem Lett. 2011 Jun 1;21(11):3404-6. | ||||
| REF 8 | Structure-Guided Design of Substituted Biphenyl Butanoic Acid Derivatives as Neprilysin Inhibitors. ACS Med Chem Lett. 2020 Jan 27;11(2):188-194. | ||||
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