7ZRA | pdb_00007zra

Crystal structure of E.coli LexA in complex with nanobody NbSOS1(Nb14497)

PDB DOI: https://doi.org/10.2210/pdb7ZRA/pdb

Classification: TRANSCRIPTION
Organism(s): Escherichia coli, Lama glama
Expression System: Escherichia coli BL21, Escherichia coli W
Mutation(s): No

Deposited: 2022-05-04 Released: 2022-10-26
Deposition Author(s): Maso, L., Vascon, F., Chinellato, M., Pardon, E., Steyaert, J., Angelini, A., Tondi, D., Cendron, L.
Funding Organization(s): Italian Ministry of Education

Experimental Data Snapshot

Method: X-RAY DIFFRACTION
Resolution: 2.80 Å
R-Value Free:
0.259 (Depositor), 0.260 (DCC)
R-Value Work:
0.223 (Depositor), 0.220 (DCC)

Starting Model: experimental
View more details

wwPDB Validation 3D Report Full Report

This is version 1.3 of the entry. See complete history.

Literature

Nanobodies targeting LexA autocleavage disclose a novel suppression strategy of SOS-response pathway.

Maso, L., Vascon, F., Chinellato, M., Goormaghtigh, F., Bellio, P., Campagnaro, E., Van Melderen, L., Ruzzene, M., Pardon, E., Angelini, A., Celenza, G., Steyaert, J., Tondi, D., Cendron, L.

(2022) Structure 30: 1479

PubMed: 36240773 Search on PubMed
DOI: https://doi.org/10.1016/j.str.2022.09.004
Primary Citation of Related Structures:
7B5G, 7OCJ, 7ZRA

PubMed Abstract:
Antimicrobial resistance threatens the eradication of infectious diseases and impairs the efficacy of available therapeutics. The bacterial SOS pathway is a conserved response triggered by genotoxic stresses and represents one of the principal mechanisms that lead to resistance. The RecA recombinase acts as a DNA-damage sensor inducing the autoproteolysis of the transcriptional repressor LexA, thereby derepressing SOS genes that mediate DNA repair, survival to chemotherapy, and hypermutation. The inhibition of such pathway represents a promising strategy for delaying the evolution of antimicrobial resistance. We report the identification, via llama immunization and phage display, of nanobodies that bind LexA with sub-micromolar affinity and block autoproteolysis, repressing SOS response in Escherichia coli. Biophysical characterization of nanobody-LexA complexes revealed that they act by trapping LexA in an inactive conformation and interfering with RecA engagement. Our studies pave the way to the development of new-generation antibiotic adjuvants for the treatment of bacterial infections.

Organizational Affiliation

Dipartimento di Biologia, Università degli Studi di Padova, Via Ugo Bassi 58/b, 35131 Padova, Italy.

Macromolecule Content

Total Structure Weight: 148.13 kDa
Atom Count: 7,783
Modelled Residue Count: 1,001
Deposited Residue Count: 1,336
Unique protein chains: 2

Macromolecules

Find similar proteins by:

(by identity cutoff) | 3D Structure

Entity ID: 1
Molecule	Chains	Sequence Length	Organism	Details	Image
LexA repressor	A, B [auth C], E [auth B], F [auth D]	202	Escherichia coli	Mutation(s): 0 Gene Names: lexA_1, lexA, lexA_2, lexA_3, lexA_4, lexA_5, lexA_6, A6581_03840, A6592_09000, A6V01_14725... lexA_1, lexA, lexA_2, lexA_3, lexA_4, lexA_5, lexA_6, A6581_03840, A6592_09000, A6V01_14725, A8C65_05740, A9819_23115, A9P13_24790, A9R57_24265, A9X72_23540, AAW05_04940, AC067_05020, AC789_1c44530, ACN002_4144, ACN68_15885, ACN81_05765, ACU57_23725, ACU90_04800, AJ318_13980, AM270_18420, AM446_25905, AM464_13585, AM465_02855, AMK83_25365, AML07_00445, AML35_16500, APT94_01725, APU18_20100, APZ14_12275, ARC77_17360, AU473_00505, AUQ13_09675, AUS26_09870, AW059_18350, AW106_02825, AWB10_24615, AWE53_003010, AWF59_006810, AWG78_010890, AWG90_025185, AWP75_14755, AZZ83_003567, B6V57_23175, B7C53_16050, B9M99_07260, B9N33_14930, B9T59_11225, BANRA_02722, BANRA_02895, BANRA_05124, BB545_04745, BE963_11630, BEN53_25180, BER14_12995, BFD68_07790, BHF03_13425, BHF46_15090, BHJ80_01810, BHS81_24295, BHS87_22640, BIQ87_23185, BIU72_20655, BIZ41_02125, BJJ90_24770, BK248_24315, BK292_01025, BK296_23860, BK334_08815, BK373_03960, BK375_08450, BK383_21615, BMA87_07675, BMT49_20690, BMT91_12915, BN17_40181, BOH76_06090, BON63_06530, BON65_23060, BON66_03315, BON69_22095, BON71_16410, BON75_07080, BON76_04855, BON83_16235, BON86_25705, BON87_02545, BON91_12300, BON92_17725, BON94_08075, BON95_04860, BON96_03145, BON98_14025, BTQ04_27960, BTQ06_28255, BUE81_22465, BvCms12BK_04297, BvCms2454_00415, BvCms28BK_01342, BvCms35BK_01831, BvCmsC61A_01832, BvCmsHHP001_00842, BvCmsHHP019_03449, BvCmsHHP056_02653, BvCmsKKP036_01653, BvCmsKKP061_03212, BvCmsKSNP073_04428, BvCmsKSNP081_02209, BvCmsKSNP120_00016, BvCmsKSP011_01869, BvCmsKSP024_01390, BvCmsKSP026_03995, BvCmsKSP045_02606, BvCmsKSP058_01651, BvCmsKSP067_03973, BvCmsKSP076_00063, BvCmsNSNP036_01892, BvCmsNSP006_05193, BvCmsNSP007_02439, BvCmsNSP047_02150, BvCmsNSP072_02985, BvCmsOUP014_01488, BvCmsSINP011_01581, BvCmsSINP022_02516, BvCmsSIP019_02982, BvCmsSIP044_03653, BVL39_05000, BW690_17275, BWI89_17045, BWP17_09115, BXT93_20190, BZL31_27495, BZL69_04975, C2M16_18650, C2U48_12390, C4K41_22540, C4M78_06355, C5715_10070, C5F72_25480, C5F73_24600, C5N07_20195, C5P01_10950, C5P44_17630, C6669_07275, C6B13_20680, C7235_23375, C7B02_13860, C7B06_21440, C7B07_20950, C7B08_17115, C7B18_19350, C9098_11905, C9114_00185, C9141_04535, C9160_08095, C9162_23740, C9201_06385, C9306_11555, C9E25_05905, C9E67_28315, C9Z03_09215, C9Z23_10210, C9Z28_18985, C9Z29_15625, C9Z37_11110, C9Z39_12685, C9Z43_13055, C9Z68_12230, C9Z69_10275, C9Z70_15630, C9Z78_21525, C9Z89_05965, CA593_05680, CCZ14_07840, CDC27_21910, CDL37_20795, CF006_04145, CG692_11650, CI641_013760, CI693_02120, CI694_23155, CIG45_19390, CJU63_23870, CJU64_24205, CMR93_13445, CO706_19840, COD30_15395, COD46_18700, CQP61_25715, CR538_23835, CR539_02040, CRD98_27320, CRE06_21195, CRJUMX01_510039, CRM83_18295, CRT43_24270, CRX46_18555, CSB64_02010, CT146_24150, CUB99_11400, CV83915_01994, CVH05_06385, CWM24_08770, CWS33_15975, D0X26_12200, D1912_18705, D2184_21525, D2185_07080, D2188_17815, D3821_04640, D3822_08745, D3M98_15580, D3O91_19225, D3P01_12220, D3P02_10990, D4011_20000, D4023_17595, D4074_20080, D4628_12380, D4636_09720, D4638_24525, D4660_19160, D4718_13325, D4L91_18735, D4M06_19695, D4M76_10435, D4U49_11220, D4U85_19640, D4V08_08845, D5H35_01910, D5I97_18270, D6004_01850, D6C36_19740, D6D43_19725, D6T60_08900, D6T98_07050, D6W00_08775, D6X36_02250, D6X63_25780, D6X76_22790, D7K33_19360, D7K63_02835, D7K66_21305, D7W70_12300, D7Y10_01185, D7Z75_09495, D8Y65_18220, D9610_00735, D9C99_09310, D9D20_17210, D9D33_01860, D9D43_18385, D9D44_06445, D9D94_04730, D9E13_11180, D9E19_14095, D9E34_02075, D9E35_10415, D9E49_22250, D9E73_19440, D9F17_19275, D9F32_11525, D9F87_12490, D9G11_22460, D9G29_18660, D9G42_14820, D9G48_15290, D9G69_15475, D9G95_21630, D9H10_15220, D9H36_09830, D9H53_20975, D9H68_20260, D9H70_15350, D9H94_14230, D9I18_21060, D9I20_19240, D9I87_21035, D9I88_03895, D9I97_23010, D9J03_04410, D9J11_07590, D9J44_17675, D9J46_13285, D9J52_18345, D9J58_14965, D9J60_05135, D9J63_12310, D9J78_21390, D9K02_09285, D9K48_05710, D9K54_02940, D9L89_19960, D9L99_05045, D9S45_16730, D9X77_17715, D9X97_19985, D9Z28_19505, DAH18_17020, DAH26_23105, DAH30_16750, DAH32_05100, DAH34_09745, DAH37_23000, DAH43_08050, DB359_22770, DBQ99_24230, DD762_09570, DEN86_01240, DEN89_16940, DEN97_12815, DEO04_14355, DEO19_12485, DEO20_13045, DIV22_28315, DJ487_17695, DJ503_03205, DK132_10450, DL251_19160, DL257_06320, DL292_14670, DL326_18360, DL455_17780, DL479_04890, DL530_02190, DL545_23320, DL705_06290, DL800_28030, DL979_22465, DLT82_16100, DLU50_04305, DLU67_12520, DLU82_06835, DLW60_00780, DLW88_15040, DLX38_07225, DLX40_14200, DLY41_09575, DLY44_12300, DM102_07955, DM129_07275, DM155_00780, DM267_22275, DM272_08145, DM280_16450, DM296_05455, DM382_06365, DM820_11410, DM962_16745, DM973_17240, DMI04_18725, DMI53_18525, DMO02_19335, DMY83_08280, DMZ50_11405, DN627_13770, DN660_12190, DN700_09495, DN703_20325, DN808_20920, DNB37_17705, DNC98_13900, DND16_08380, DND79_11485, DNI21_02325, DNJ62_19610, DNK12_18155, DNQ45_03405, DNR35_06920, DNR41_16590, DNW42_02895, DNX19_05225, DOE35_19020, DOM23_10665, DOS18_18880, DOT81_19955, DOU81_18220, DOY22_18350, DOY56_18570, DOY61_11305, DOY67_06200, DP258_12750, DP265_01880, DP277_17730, DQE91_14650, DQF36_19215, DQF57_12540, DQF71_02370, DQF72_01950, DQG35_19915, DQO13_07445, DQP61_07285, DRP48_19990, DRW19_10040, DS143_02030, DS721_17960, DS732_01915, DS966_07340, DT034_16995, DTL43_19530, DTL90_18345, DTM10_17250, DTM45_22000, DTZ20_07940, DU309_08590, DU321_20700, DU333_20915, DVB38_00780, DW236_20350, DWB25_23105, DXT69_11240, DXT71_13455, DXT73_06680, DXX80_014420, E0I42_01715, E0K84_14705, E0L04_06555, E0L12_12475, E2112_13635, E2119_15925, E2127_04695, E2128_24955, E2129_11665, E2134_19225, E2135_15890, E2148_17730, E2855_05069, E2863_04868, E4A44_08405, E4K51_08400, E4K55_09280, E4K59_02705, E4K60_21225, E4K61_06350, E5P22_21020, E5P24_22750, E5P28_22440, E5P37_19690, E5S42_14590, E5S56_16625, E5S58_10005, E5S61_13810, E5S62_09140, EA159_09860, EA164_11895, EA167_12330, EA174_06160, EA184_14750, EA189_16420, EA191_11120, EA198_19920, EA200_15705, EA203_12170, EA213_12715, EA214_12670, EA218_06700, EA222_18665, EA223_05425, EA225_15150, EA231_21330, EA232_11815, EA233_13540, EA235_13150, EA239_14350, EA242_15215, EA245_21190, EA247_19925, EA250_22905, EA410_10735, EA429_14660, EA433_09295, EA434_07730, EA435_14070, EA834_14185, EAI42_11775, EAI46_13910, EAI52_14305, EAM59_19660, EAN70_04295, EAN77_18045, EAX79_14320, EB476_06510, EB509_23270, EB510_19485, EB515_21475, EB525_RS22295, EBA46_21785, EBA84_21540, EBJ06_20090, EBM08_00725, EC1094V2_4222, EC3234A_77c00360, EC3426_00367, EC382_06195, EC95NR1_03586, ECONIH1_23895, ECs5026, ECTO124_04687, ECTO6_04452, ED178_02160, ED225_20150, ED307_20800, ED600_11955, ED607_20180, ED611_21565, ED648_10135, ED903_21355, ED944_20920, EEA45_23665, EEP23_23665, EF082_14250, EF173_02775, EG075_18135, EG599_11110, EG796_08865, EG808_11410, EGC26_22390, EGT48_16960, EGU87_16570, EH186_18415, EH412_04435, EHD45_05640, EHD63_19000, EHD79_12175, EHH55_01035, EHJ36_05660, EHJ66_21070, EHV81_14020, EHV90_14340, EHW09_21540, EHX09_18295, EI021_16120, EI028_05870, EI032_15785, EI041_04290, EIA08_19795, EIA21_16610, EIZ93_23270, EJ366_21585, EJC75_19935, EKI52_13610, EL75_4145, EL79_4350, EL80_4257, ELT17_04335, ELT20_15125, ELT22_19765, ELT23_17595, ELT33_14365, ELT48_13885, ELT49_00210, ELT58_16885, ELU82_17295, ELU85_16290, ELU96_14010, ELV00_20075, ELV05_04290, ELV08_22365, ELV13_10080, ELV15_24385, ELV22_20245, ELV24_10490, ELV28_08325, ELX56_12745, ELX70_12445, ELX76_18040, ELX79_01350, ELX83_19330, ELY05_20415, ELY23_17950, ELY24_02305, ELY41_24075, ELY48_01785, ELY50_17875, EO241_22225, EPS91_05510, EPS94_15340, EPU41_22875, EQ820_09870, EQ823_07865, EQ825_11565, EQ830_09950, EQO00_24610, ERL57_14825, ERS085365_02976, ERS085366_03456, ERS085374_01624, ERS085379_03983, ERS085383_01448, ERS085386_02660, ERS085404_01243, ERS085406_04198, ERS085411_04446, ERS085416_00631, ERS139211_04672, ERS150873_01187, ERS150876_04135, EST51_23545, EVY14_11520, EWK56_09425, EXM29_06605, ExPECSC019_02605, ExPECSC038_04549, ExPECSC065_01920, EXX06_18435, EXX13_12090, EXX23_19315, EXX24_09955, EXX53_09260, EXX55_18970, EXX71_07865, EXX78_13230, EXX87_20000, EYD11_21280, EYX82_05305, EYX99_01640, EYY27_19365, EYY34_21065, EYY78_21440, F1E13_08855, F1E19_14155, F7F00_04830, F7F11_03715, F7F18_10310, F7F23_02515, F7F26_18655, F7F29_21255, F7F56_09730, F7G01_19665, F7G03_07710, F9040_10620, F9050_18985, F9225_08300, F9B07_06640, F9X20_06245, F9Z53_12245, F9Z74_02500, FAF34_027445, FE846_20710, FKO60_19090, FNJ67_24760, FNJ69_19430, FNJ83_25115, FORC82_4459, FPI65_24840, FQ021_13785, FQ022_13220, FQ915_20070, FQR64_21510, FQU83_25315, FQZ46_11420, FRV13_15940, FTV92_16270, FTV93_16625, FV293_00180, FV295_14155, FV438_02950, FVB16_13290, FY127_04780, FZ043_01435, FZC17_04895, FZN06_07660, FZN26_04905, FZN30_09565, G3565_23685, G3V64_10445, G5603_20840, G5608_21780, G5616_05135, G5632_08040, G5668_16270, G5670_04760, G5675_07615, G5680_02920, G5686_19405, G5688_11635, G5696_16625, G5697_10455, GFU40_20155, GFU45_18365, GFU47_11010, GHR40_03285, GII67_18535, GII91_01590, GIJ01_07080, GIY13_22705, GIY19_15100, GJ11_25525, GJ638_08800, GJD97_25670, GKE15_08795, GKE16_10270, GKE22_09815, GKE24_10940, GKE26_10295, GKE29_07830, GKE31_09080, GKE39_08675, GKE46_08475, GKE53_08285, GKE58_08305, GKE60_08375, GKE64_08350, GKE69_08185, GKE77_10555, GKE79_08190, GKE87_03580, GKE92_11980, GKE93_09555, GKE98_17470, GKF00_11225, GKF03_07640, GKF21_19525, GKF28_19545, GKF34_19920, GKF39_10130, GKF47_19635, GKF52_19185, GKF74_07005, GKF86_09530, GKF89_08240, GKG08_19925, GKG09_19795, GKG11_19965, GKG12_13240, GKG22_19630, GKG29_19840, GN312_11355, GNZ00_12570, GNZ02_08260, GNZ03_05545, GNZ05_23055, GP650_09375, GP654_14900, GP661_10840, GP662_05880, GP664_12905, GP666_14410, GP671_00680, GP678_14315, GP689_08955, GP698_02940, GP700_05045, GP711_15355, GP712_07365, GP720_18065, GP727_20045, GP892_04865, GP912_08340, GP935_16255, GP945_10980, GP946_12270, GP950_01700, GQA23_07565, GQA63_11350, GQA64_11565, GQE22_22480, GQE30_09515, GQE33_21095, GQE34_18985, GQE36_21390, GQE42_17480, GQE47_16615, GQE51_19030, GQE58_14030, GQE64_15035, GQE68_09185, GQE87_13955, GQE88_20795, GQE93_06065, GQF59_13075, GQL64_02840, GQM04_21825, GQM06_05485, GQM09_07375, GQM10_00185, GQM13_10075, GQM17_17755, GQM18_21055, GQM28_14230, GQN16_10665, GQN24_10350, GQN33_15605, GQS26_13850, GQY14_18825, GRW05_25935, GRW12_07495, GRW27_03680, GRW30_10035, GRW42_18565, GRW57_21705, GRW80_00680, GRW81_20425, GUB08_14505, GUB85_10045, GUB91_12015, GUB95_13125, GUC01_08305, GUC12_14155, GUC40_13020, GUI16_13780, GUI33_07450, GZS12_22285, HmCms169_03196, HmCms184_01443, HmCmsJML074_03763, HmCmsJML079_02438, HmCmsJML146_04299, HmCmsJML204_02607, HmCmsJML236_03697, HMPREF3040_01362, HW43_01890, MJ49_09110, MS6198_46970, MS8345_04507, NCTC10082_02015, NCTC10089_04675, NCTC10090_02705, NCTC10764_02888, NCTC10766_00857, NCTC10767_00646, NCTC10963_04726, NCTC10974_05266, NCTC11022_04367, NCTC11126_02097, NCTC11181_01887, NCTC11341_02866, NCTC12650_04928, NCTC12950_05138, NCTC13127_06081, NCTC13216_02170, NCTC13846_04407, NCTC7922_05075, NCTC7927_05177, NCTC7928_03743, NCTC8009_08326, NCTC8179_05022, NCTC8621_04799, NCTC8959_04132, NCTC8960_02264, NCTC8985_03936, NCTC9001_04561, NCTC9007_01043, NCTC9036_04577, NCTC9044_02378, NCTC9045_05471, NCTC9050_02746, NCTC9055_01590, NCTC9058_02211, NCTC9062_03515, NCTC9073_00755, NCTC9077_05829, NCTC9081_06397, NCTC9111_04889, NCTC9117_05822, NCTC9119_04984, NCTC9434_04602, NCTC9701_04926, NCTC9702_05565, NCTC9703_04146, NCTC9706_01937, NCTC9777_01051, NCTC9962_03719, NCTC9969_04855, PGD_03216, PU06_05790, RG28_25645, RK56_017085, RX35_03825, SAMEA3472043_01946, SAMEA3472044_04487, SAMEA3472047_04009, SAMEA3472055_01604, SAMEA3472056_04390, SAMEA3472070_04043, SAMEA3472080_00231, SAMEA3472090_02852, SAMEA3472108_01696, SAMEA3472110_00875, SAMEA3472112_01208, SAMEA3472114_02039, SAMEA3472147_04803, SAMEA3484427_03830, SAMEA3484429_02475, SAMEA3484434_03756, SAMEA3485101_02956, SAMEA3752372_01305, SAMEA3752553_02498, SAMEA3752557_02189, SAMEA3752559_00285, SAMEA3752620_03709, SAMEA3753064_01449, SAMEA3753097_04412, SAMEA3753164_04167, SAMEA3753290_01938, SAMEA3753300_00786, SK85_04379, SY51_23235, U12A_04345, U14A_04341, UC41_10590, UN86_02805, UN91_08555, WQ89_14700, WR15_07670, YDC107_2768 EC: 3.4.21.88
UniProt
Find proteins for C3SHL2 (Escherichia coli) Explore C3SHL2 Go to UniProtKB: C3SHL2
Entity Groups
Sequence Clusters	30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt Group	C3SHL2
Sequence Annotations Expand
Reference Sequence LOADING

Find similar proteins by:

(by identity cutoff) | 3D Structure

Entity ID: 2
Molecule	Chains	Sequence Length	Organism	Details	Image
Nanobody NbSOS1 (Nb14497)	C [auth E], D [auth G], G [auth F], H	132	Lama glama	Mutation(s): 0
Entity Groups
Sequence Clusters	30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
Sequence Annotations Expand
Reference Sequence LOADING

Small Molecules

Ligands 1 Unique
ID	Chains	Name / Formula / InChI Key	2D Diagram	3D Interactions
EDO Query on EDO Download Ideal Coordinates CCD File SDF format, chain I [auth A] SDF format, chain J [auth C] SDF format, chain K [auth C] MOL2 format, chain I [auth A] MOL2 format, chain J [auth C] MOL2 format, chain K [auth C] mmCIF format, chain I [auth A] mmCIF format, chain J [auth C] mmCIF format, chain K [auth C]	I [auth A], J [auth C], K [auth C]	1,2-ETHANEDIOL C₂ H₆ O₂ LYCAIKOWRPUZTN-UHFFFAOYSA-N		Interactions Focus chain I [auth A] Focus chain J [auth C] Focus chain K [auth C] Interactions & Density Focus chain I [auth A] Focus chain J [auth C] Focus chain K [auth C]