Binding Site Information of Target
| Target General Information | Top | ||||
|---|---|---|---|---|---|
| Target ID | T86773 | Target Info | |||
| Target Name | ATP-dependent protease Lon (LONP1) | ||||
| Synonyms | Serine protease 15; Mitochondrial ATP-dependent protease Lon; Lon protease-like protein; LONP1; LONP; LONHs | ||||
| Target Type | Literature-reported Target | ||||
| Gene Name | LONP1 | ||||
| Biochemical Class | Peptidase | ||||
| UniProt ID | |||||
| Drug Binding Sites of Target | Top | |||||
|---|---|---|---|---|---|---|
| Ligand Name: Adenosine triphosphate | Ligand Info | |||||
| Structure Description | Human mitochondrial Lon protease with substrate in the ATPase domain | PDB:7P09 | ||||
| Method | Electron microscopy | Resolution | 2.70 Å | Mutation | No | [1] |
| PDB Sequence |
EKDDKDAIEE
419 KFRERLKELV429 VPKHVMDVVD439 EELSKLGLLD449 NHSSEFNVTR459 NYLDWLTSIP 469 WGKYSNENLD479 LARAQAVLEE489 DHYGMEDVKK499 RILEFIAVSQ509 LRGSTQGKIL 519 CFYGPPGVGK529 TSIARSIARA539 LNREYFRFSV549 GGMTDVAEIK559 GHRRTYVGAM 569 PGKIIQCLKK579 TKTENPLILI589 DEVDKIGRGY599 QGDPSSALLE609 LLDPEQNANF 619 LDHYLDVPVD629 LSKVLFICTA639 NVTDTIPEPL649 RDRMEMINVS659 GYVAQEKLAI 669 AERYLVPQAR679 ALCGLDESKA689 KLSSDVLTLL699 IKQYCRESGV709 RNLQKQVEKV 719 LRKSAYKIVS729 GEAESVEVTP739 ENLQDFVGKP749 VFTVERMYDV759 TPPGVVMGLA 769 WTAMGGSTLF779 VETSLRRPGD795 KDGSLEVTGQ805 LGEVMKESAR815 IAYTFARAFL 825 MQHAPANDYL835 VTSHIHLHVP845 EGATPKDGPS855 AGCTIVTALL865 SLAMGRPVRQ 875 NLAMTGEVSL885 TGKILPVGGI895 KEKTIAAKRA905 GVTCIVLPAE915 NKKDFYDLAA 925 FITEGLEVHF935 VEHYREIFDI945 AFPD
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ASP490
4.286
HIS491
3.748
TYR492
2.703
GLY493
4.929
MET494
3.997
PRO524
3.979
PRO525
3.266
GLY526
2.845
VAL527
3.006
GLY528
2.968
LYS529
2.895
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| Click to View More Binding Site Information of This Target and Ligand Pair | ||||||
| Ligand Name: Bortezomib | Ligand Info | |||||
| Structure Description | Lon protease proteolytic domain complexed with bortezomib | PDB:6X27 | ||||
| Method | X-ray diffraction | Resolution | 2.12 Å | Mutation | No | [2] |
| PDB Sequence |
ERMYDVTPPG
763 VVMGLAWTAM773 GGSTLFVETS783 LRRPDGSLEV802 TGQLGEVMKE812 SARIAYTFAR 822 AFLMQHAPAN832 DYLVTSHIHL842 HVPEGATPKD852 GPSAGCTIVT862 ALLSLAMGRP 872 VRQNLAMTGE882 VSLTGKILPV892 GGIKEKTIAA902 KRAGVTCIVL912 PAENKKDFYD 922 LAAFITEGLE932 VHFVEHYREI942 FDIAFP
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| Click to View More Binding Site Information of This Target and Ligand Pair | ||||||
| Ligand Name: adenosine diphosphate | Ligand Info | |||||
| Structure Description | Substrate-free human mitochondrial LONP1 | PDB:7KSL | ||||
| Method | Electron microscopy | Resolution | 3.50 Å | Mutation | No | [3] |
| PDB Sequence |
FRERLKELVV
430 PKHVMDVVDE440 ELSKLGLLDN450 HSSEFNVTRN460 YLDWLTSIPW470 GKYSNENLDL 480 ARAQAVLEED490 HYGMEDVKKR500 ILEFIAVSQL510 RGSTQGKILC520 FYGPPGVGKT 530 SIARSIARAL540 NREYFRFSVG550 GMTDVAEIGK572 IIQCLKKTKT582 ENPLILIDEV 592 DKIPSSALLE609 LLDPEQNANF619 LDHYLDVPVD629 LSKVLFICTA639 NVTDTIPEPL 649 RDRMEMINVS659 GYVAQEKLAI669 AERYLVPQAR679 ALCGLDESSS693 DVLTLLIKQY 703 CRESGVRNLQ713 KQVEKVLRKS723 AYKIVSGENL742 QDFVGKPVFT752 VERMYDVTPP 762 GVVMGLAWTA772 MGGSTLFVET782 SLRRPQDKDG798 SLEVTGQLGE808 VMKESARIAY 818 TFARAFLMQH828 APANDYLVTS838 HIHLHVPEGA848 TPKDGPSAGC858 TIVTALLSLA 868 MGRPVRQNLA878 MTGEVSLTGK888 ILPVGGIKEK898 TIAAKRAGVT908 CIVLPAENKK 918 DFYDLAAFIT928 EGLEVHFVEH938 YREIFDIAF
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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 .ADP or .ADP2 or .ADP3 or :3ADP;style chemicals stick;color identity;select .C:490 or .C:491 or .C:492 or .C:494 or .C:524 or .C:525 or .C:526 or .C:527 or .C:528 or .C:529 or .C:530 or .C:531 or .C:638 or .C:661 or .C:669 or .C:673 or .C:709 or .C:713; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| Click to View More Binding Site Information of This Target and Ligand Pair | ||||||
| Ligand Name: Phosphothiophosphoric acid-adenylate ester | Ligand Info | |||||
| Structure Description | P1a-state of wild type human mitochondrial LONP1 protease with bound substrate protein and ATPgS | PDB:7NFY | ||||
| Method | Electron microscopy | Resolution | 3.90 Å | Mutation | No | [4] |
| PDB Sequence |
HLPLIAITRN
132 PVFPRFIKII142 EVKNKKLVEL152 LRRKVRLAQP162 YVGVFLKRDD172 SNESDVVESL 182 DEIYHTGTFA192 QIHEMQDLGD202 KLRMIVMGHR212 RVHISRQLEM272 VEVENVVHED 282 FQVTEEVKAL292 TAEIVKTIRD302 IIALNPLYRE312 SVLQMMQAGQ322 RVVDNPIYLS 332 DMGAALTGAE342 SHELQDVLEE352 TNIPKRLYKA362 LSLLKKEFEL372 SKLQQRLGRE 382 VEEKIKQTHR392 KYLLQEQLKI402 IKKELGLEKD412 DKDAIEEKFR422 ERLKELVVPK 432 HVMDVVDEEL442 SKLGLLDNHS452 SEFNVTRNYL462 DWLTSIPWGK472 YSNENLDLAR 482 AQAVLEEDHY492 GMEDVKKRIL502 EFIAVSQLRG512 STQGKILCFY522 GPPGVGKTSI 532 ARSIARALNR542 EYFRFSVGGM552 TDVAEIKGHR562 RTYVGAMPGK572 IIQCLKKTKT 582 ENPLILIDEV592 DKIGRGYQGD602 PSSALLELLD612 PEQNANFLDH622 YLDVPVDLSK 632 VLFICTANVT642 DTIPEPLRDR652 MEMINVSGYV662 AQEKLAIAER672 YLVPQARALC 682 GLDESKAKLS692 SDVLTLLIKQ702 YCRESGVRNL712 QKQVEKVLRK722 SAYKIVSGEA 732 ESVEVTPENL742 QDFVGKPVFT752 VERMYDVTPP762 GVVMGLAWTA772 MGGSTLFVET 782 SLRRPQDKDA792 KGDKDGSLEV802 TGQLGEVMKE812 SARIAYTFAR822 AFLMQHAPAN 832 DYLVTSHIHL842 HVPEGATPKD852 GPSAGCTIVT862 ALLSLAMGRP872 VRQNLAMTGE 882 VSLTGKILPV892 GGIKEKTIAA902 KRAGVTCIVL912 PAENKKDFYD922 LAAFITEGLE 932 VHFVEHYREI942 FDIAFP
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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 .AGS or .AGS2 or .AGS3 or :3AGS;style chemicals stick;color identity;select .A:490 or .A:491 or .A:492 or .A:493 or .A:494 or .A:524 or .A:525 or .A:526 or .A:527 or .A:528 or .A:529 or .A:530 or .A:531 or .A:532 or .A:638 or .A:640 or .A:661 or .A:669 or .A:673 or .A:674 or .A:677 or .A:709 or .A:710 or .A:713; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
ASP490
4.230
HIS491
2.232
TYR492
2.148
GLY493
4.263
MET494
2.573
PRO524
4.075
PRO525
2.964
GLY526
1.870
VAL527
2.552
GLY528
2.302
LYS529
1.932
THR530
2.242
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| Ligand Name: ((R)-3-Methyl-1-((R)-3-phenyl-2-(pyrazine-2-carboxamido)propanamido)butyl)boronic acid | Ligand Info | |||||
| Structure Description | Lon protease proteolytic domain | PDB:6WZV | ||||
| Method | X-ray diffraction | Resolution | 2.51 Å | Mutation | No | [2] |
| PDB Sequence |
ERMYDVTPPG
763 VVMGLAWTAM773 GGSTLFVETS783 LRRPDGSLEV802 TGQLGEVMKE812 SARIAYTFAR 822 AFLMQHAPAN832 DYLVTSHIHL842 HVPEGATPKD852 GPSAGCTIVT862 ALLSLAMGRP 872 VRQNLAMTGE882 VSLTGKILPV892 GGIKEKTIAA902 KRAGVTCIVL912 PAENKKDFYD 922 LAAFITEGLE932 VHFVEHYREI942 FDIAFPDEQA952 EALAV
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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 .UFY or .UFY2 or .UFY3 or :3UFY;style chemicals stick;color identity;select .A:768 or .A:769 or .A:770 or .A:771 or .A:772 or .A:778 or .A:810 or .A:850 or .A:851 or .A:852 or .A:853 or .A:854 or .A:855 or .A:856 or .A:880 or .A:892 or .A:893 or .A:898; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| Ligand Name: ((R)-4-Phenyl-1-((R)-2-(pyrazine-2-carboxamido)pentanamido)butyl)boronic acid | Ligand Info | |||||
| Structure Description | Lon protease proteolytic domain complexed with covalent boronic acid inhibitor | PDB:6X1M | ||||
| Method | X-ray diffraction | Resolution | 3.51 Å | Mutation | No | [2] |
| PDB Sequence |
ERMYDVTPPG
763 VVMGLAWTAM773 GGSTLFVETS783 LRRPDGSLEV802 TGQLGEVMKE812 SARIAYTFAR 822 AFLMQHAPAN832 DYLVTSHIHL842 HVPEGATPKD852 GPSAGCTIVT862 ALLSLAMGRP 872 VRQNLAMTGE882 VSLTGKILPV892 GGIKEKTIAA902 KRAGVTCIVL912 PAENKKDFYD 922 LAAFITEGLE932 VHFVEHYREI942 FDIAFPDEQA952 EALAVE
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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 .UKS or .UKS2 or .UKS3 or :3UKS;style chemicals stick;color identity;select .A:767 or .A:768 or .A:769 or .A:770 or .A:771 or .A:772 or .A:778 or .A:779 or .A:780 or .A:810 or .A:844 or .A:849 or .A:850 or .A:851 or .A:852 or .A:853 or .A:854 or .A:855 or .A:856 or .A:859 or .A:880 or .A:892 or .A:893 or .A:898; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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GLY767
2.714
LEU768
3.333
ALA769
2.727
TRP770
2.247
THR771
3.731
ALA772
4.535
LEU778
2.688
PHE779
4.790
VAL780
2.939
MET810
3.056
VAL844
2.856
THR849
3.940
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| References | Top | ||||
|---|---|---|---|---|---|
| REF 1 | A dual allosteric pathway drives human mitochondrial Lon | ||||
| REF 2 | Structure-Based Design of Selective LONP1 Inhibitors for Probing In Vitro Biology. J Med Chem. 2021 Apr 22;64(8):4857-4869. | ||||
| REF 3 | Structures of the human LONP1 protease reveal regulatory steps involved in protease activation. Nat Commun. 2021 May 28;12(1):3239. | ||||
| REF 4 | Catalytic cycling of human mitochondrial Lon protease. Structure. 2022 Sep 1;30(9):1254-1268.e7. | ||||
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