Target Binding Site Detail
| 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 | |||||
| Ligand General Information | Top | ||||
|---|---|---|---|---|---|
| Ligand Name | Adenosine triphosphate | Ligand Info | |||
| Canonical SMILES | C1=NC(=C2C(=N1)N(C=N2)C3C(C(C(O3)COP(=O)(O)OP(=O)(O)OP(=O)(O)O)O)O)N | ||||
| InChI | 1S/C10H16N5O13P3/c11-8-5-9(13-2-12-8)15(3-14-5)10-7(17)6(16)4(26-10)1-25-30(21,22)28-31(23,24)27-29(18,19)20/h2-4,6-7,10,16-17H,1H2,(H,21,22)(H,23,24)(H2,11,12,13)(H2,18,19,20)/t4-,6-,7-,10-/m1/s1 | ||||
| InChIKey | ZKHQWZAMYRWXGA-KQYNXXCUSA-N | ||||
| PubChem Compound ID | 5957 | ||||
| Drug Binding Sites of Target | Top | |||||
|---|---|---|---|---|---|---|
| PDB ID: 7P0M Human mitochondrial Lon protease with substrate in the ATPase and protease domains | ||||||
| Method | Electron microscopy | Resolution | 2.75 Å | Mutation | Yes | [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 KEATIAAKRA905 GVTCIVLPAE915 NKKDFYDLAA 925 FITEGLEVHF935 VEHYREIFDI945 AFPD
|
|||||
|
|
ASP490
4.171
HIS491
3.479
TYR492
2.554
GLY493
4.758
MET494
3.817
PRO524
3.924
PRO525
3.343
GLY526
2.889
VAL527
2.993
GLY528
3.268
LYS529
2.950
|
|||||
| PDB ID: 7P09 Human mitochondrial Lon protease with substrate in the ATPase domain | ||||||
| Method | Electron microscopy | Resolution | 2.70 Å | Mutation | No | [2] |
| 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
|
|||||
| PDB ID: 7NG5 P1c-state of wild type human mitochondrial LONP1 protease with bound substrate protein in presence of ATP/ADP mix | ||||||
| Method | Electron microscopy | Resolution | 3.80 Å | Mutation | No | [3] |
| 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
|
|||||
|
|
ASP490
2.966
HIS491
2.452
TYR492
2.485
GLY493
4.512
MET494
2.361
PRO524
4.697
PRO525
2.967
GLY526
2.046
VAL527
2.625
GLY528
2.389
LYS529
1.772
THR530
1.855
|
|||||
| PDB ID: 7NG4 P1b-state of wild type human mitochondrial LONP1 protease with bound endogenous substrate protein and in presence of ATP/ADP mix | ||||||
| Method | Electron microscopy | Resolution | 4.40 Å | Mutation | No | [3] |
| 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 .ATP or .ATP2 or .ATP3 or :3ATP;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:591 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
2.955
HIS491
2.499
TYR492
2.596
GLY493
4.656
MET494
2.335
PRO524
3.437
PRO525
2.592
GLY526
1.671
VAL527
2.275
GLY528
1.851
LYS529
1.866
THR530
1.976
|
|||||
| PDB ID: 7KRZ Human mitochondrial LONP1 in complex with Bortezomib | ||||||
| Method | Electron microscopy | Resolution | 3.20 Å | Mutation | No | [4] |
| PDB Sequence |
IEEKFRERLK
426 ELVVPKHVMD436 VVDEELSKLG446 LLDNHSSEFN456 VTRNYLDWLT466 SIPWGKYSNE 476 NLDLARAQAV486 LEEDHYGMED496 VKKRILEFIA506 VSQLRGSTQG516 KILCFYGPPG 526 VGKTSIARSI536 ARALNREYFR546 FSVGGMTDVA556 EIKGHRRTYV566 GAMPGKIIQC 576 LKKTKTENPL586 ILIDEVDKIG596 RGYQGDPSSA606 LLELLDPEQN616 ANFLDHYLDV 626 PVDLSKVLFI636 CTANVTDTIP646 EPLRDRMEMI656 NVSGYVAQEK666 LAIAERYLVP 676 QARALCGLDE686 SKAKLSSDVL696 TLLIKQYCRE706 SGVRNLQKQV716 EKVLRKSAYK 726 IVSGEAESVE736 VTPENLQDFV746 GKPVFTVERM756 YDVTPPGVVM766 GLAWTAMGGS 776 TLFVETSLRR786 PQDKDGSLEV802 TGQLGEVMKE812 SARIAYTFAR822 AFLMQHAPAN 832 DYLVTSHIHL842 HVPEGATPKD852 GPSAGCTIVT862 ALLSLAMGRP872 VRQNLAMTGE 882 VSLTGKILPV892 GGIKEKTIAA902 KRAGVTCIVL912 PAENKKDFYD922 LAAFITEGLE 932 VHFVEHYREI942 FDIAF
|
|||||
|
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .ATP or .ATP2 or .ATP3 or :3ATP;style chemicals stick;color identity;select .A:490 or .A:491 or .A:492 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:591 or .A:638 or .A:640 or .A:661 or .A:669 or .A:673 or .A:674 or .A:709 or .A:710 or .A:713; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
ASP490
4.152
HIS491
3.597
TYR492
3.083
MET494
3.763
PRO524
4.453
PRO525
3.303
GLY526
3.165
VAL527
3.196
GLY528
3.036
LYS529
2.804
THR530
2.875
|
|||||
| PDB ID: 7KSM Human mitochondrial LONP1 with endogenous substrate | ||||||
| Method | Electron microscopy | Resolution | 3.20 Å | Mutation | No | [4] |
| PDB Sequence |
AIEEKFRERL
425 KELVVPKHVM435 DVVDEELSKL445 GLLDNHSSEF455 NVTRNYLDWL465 TSIPWGKYSN 475 ENLDLARAQA485 VLEEDHYGME495 DVKKRILEFI505 AVSQLRGSTQ515 GKILCFYGPP 525 GVGKTSIARS535 IARALNREYF545 RFSVGGMTDV555 AEIKGHRRTY565 VGAMPGKIIQ 575 CLKKTKTENP585 LILIDEVDKI595 GRGYQGDPSS605 ALLELLDPEQ615 NANFLDHYLD 625 VPVDLSKVLF635 ICTANVTDTI645 PEPLRDRMEM655 INVSGYVAQE665 KLAIAERYLV 675 PQARALCGLD685 ESKAKLSSDV695 LTLLIKQYCR705 ESGVRNLQKQ715 VEKVLRKSAY 725 KIVSGEAESV735 EVTPENLQDF745 VGKPVFTVER755 MYDVTPPGVV765 MGLAWTAMGG 775 STLFVETSLR785 RPGDKDGSLE801 VTGQLGEVMK811 ESARIAYTFA821 RAFLMQHAPA 831 NDYLVTSHIH841 LHVPEGATPK851 DGPSAGCTIV861 TALLSLAMGR871 PVRQNLAMTG 881 EVSLTGKILP891 VGGIKEKTIA901 AKRAGVTCIV911 LPAENKKDFY921 DLAAFITEGL 931 EVHFVEHYRE941 IFDIAF
|
|||||
|
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .ATP or .ATP2 or .ATP3 or :3ATP;style chemicals stick;color identity;select .A:490 or .A:491 or .A:492 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:640 or .A:661 or .A:669 or .A:673 or .A:709 or .A:710; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
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| References | Top | ||||
|---|---|---|---|---|---|
| REF 1 | A dual allosteric pathway drives human mitochondrial Lon | ||||
| REF 2 | A dual allosteric pathway drives human mitochondrial Lon | ||||
| REF 3 | Catalytic cycling of human mitochondrial Lon protease. Structure. 2022 Sep 1;30(9):1254-1268.e7. | ||||
| REF 4 | Structures of the human LONP1 protease reveal regulatory steps involved in protease activation. Nat Commun. 2021 May 28;12(1):3239. | ||||
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