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- PDB-9bjh: Crystal structure of neutralizing human monoclonal antibody 75C8 ... -

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Basic information

Entry
Database: PDB / ID: 9bjh
TitleCrystal structure of neutralizing human monoclonal antibody 75C8 in complex with AMA1 DI-DII
Components
  • 75C8 Fab Heavy Chain
  • 75C8 Fab Light Chain
  • Apical membrane antigen 1
KeywordsSTRUCTURAL PROTEIN / Apical membrane antigen 1 / AMA1 / Plasmodium / Malaria / Antigen-Antibody complex
Function / homology
Function and homology information


apical complex / microneme / host cell surface binding / symbiont entry into host / membrane
Similarity search - Function
Apical membrane antigen 1 domain superfamily / Apical membrane antigen 1 / Apical membrane antigen 1 / Apical membrane antigen 1
Similarity search - Domain/homology
Apical membrane antigen 1
Similarity search - Component
Biological speciesPlasmodium falciparum 3D7 (eukaryote)
Homo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.8 Å
AuthorsPatel, P.N. / Tang, W.K. / Tolia, N.H.
Funding support United States, 1items
OrganizationGrant numberCountry
National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)1ZIAAAI001236 United States
CitationJournal: Cell Rep Med / Year: 2025
Title: A strain-transcending anti-AMA1 human monoclonal antibody neutralizes malaria parasites independent of direct RON2L receptor blockade.
Authors: Patel, P.N. / Diouf, A. / Dickey, T.H. / Tang, W.K. / Hopp, C.S. / Traore, B. / Long, C.A. / Miura, K. / Crompton, P.D. / Tolia, N.H.
History
DepositionApr 25, 2024Deposition site: RCSB / Processing site: RCSB
Revision 1.0Mar 12, 2025Provider: repository / Type: Initial release
Revision 1.1Mar 19, 2025Group: Database references / Category: citation
Item: _citation.page_first / _citation.page_last ..._citation.page_first / _citation.page_last / _citation.pdbx_database_id_PubMed / _citation.title
Revision 1.2Apr 2, 2025Group: Database references / Category: citation / Item: _citation.journal_volume

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Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

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Assembly

Deposited unit
A: Apical membrane antigen 1
B: Apical membrane antigen 1
H: 75C8 Fab Heavy Chain
I: 75C8 Fab Heavy Chain
L: 75C8 Fab Light Chain
M: 75C8 Fab Light Chain


Theoretical massNumber of molelcules
Total (without water)179,0026
Polymers179,0026
Non-polymers00
Water37821
1
A: Apical membrane antigen 1
H: 75C8 Fab Heavy Chain
L: 75C8 Fab Light Chain


Theoretical massNumber of molelcules
Total (without water)89,5013
Polymers89,5013
Non-polymers00
Water543
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
2
B: Apical membrane antigen 1
I: 75C8 Fab Heavy Chain
M: 75C8 Fab Light Chain


Theoretical massNumber of molelcules
Total (without water)89,5013
Polymers89,5013
Non-polymers00
Water362
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Unit cell
Length a, b, c (Å)54.868, 71.620, 132.927
Angle α, β, γ (deg.)94.105, 99.195, 112.393
Int Tables number1
Space group name H-MP1
Space group name HallP1
Symmetry operation#1: x,y,z

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Components

#1: Protein Apical membrane antigen 1 / Merozoite surface antigen


Mass: 39655.469 Da / Num. of mol.: 2 / Mutation: T64A, T188A, S273A, S323A, S324A
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Plasmodium falciparum 3D7 (eukaryote) / Strain: isolate 3D7 / Gene: PF3D7_1133400 / Plasmid: pHL-sec / Cell (production host): Kidney (Embryonic) / Cell line (production host): Expi293F / Production host: Homo sapiens (human) / References: UniProt: Q7KQK5
#2: Antibody 75C8 Fab Heavy Chain


Mass: 25851.980 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Plasmid: pHL-sec / Cell (production host): Kidney (Embryonic) / Cell line (production host): Expi293F / Production host: Homo sapiens (human)
#3: Antibody 75C8 Fab Light Chain


Mass: 23993.672 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Plasmid: pHL-sec / Cell (production host): Kidney (Embryonic) / Cell line (production host): Expi293F / Production host: Homo sapiens (human)
#4: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 21 / Source method: isolated from a natural source / Formula: H2O
Has protein modificationY
Sequence detailsThe author states that all N-linked glycosylation sites (NXS/T) were modified by substituting the ...The author states that all N-linked glycosylation sites (NXS/T) were modified by substituting the serine or threonine residue with an alanine residue to prevent N-linked glycosylation.

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Experimental details

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Experiment

ExperimentMethod: X-RAY DIFFRACTION / Number of used crystals: 1

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Sample preparation

CrystalDensity Matthews: 2.64 Å3/Da / Density % sol: 53.4 %
Crystal growTemperature: 291.15 K / Method: vapor diffusion, hanging drop / pH: 9.5 / Details: 50% (v/v) PEG 400, 0.2M sodium chloride, 0.1M CHES

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Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: APS / Beamline: 22-ID / Wavelength: 1 Å
DetectorType: DECTRIS EIGER X 16M / Detector: PIXEL / Date: Sep 17, 2022
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1 Å / Relative weight: 1
ReflectionResolution: 2.8→19.87 Å / Num. obs: 41930 / % possible obs: 86.57 % / Redundancy: 1.9 % / Biso Wilson estimate: 43.06 Å2 / CC1/2: 0.976 / CC star: 0.994 / Rmerge(I) obs: 0.1122 / Rpim(I) all: 0.1122 / Rrim(I) all: 0.1586 / Net I/σ(I): 3.52
Reflection shellResolution: 2.8→2.87 Å / Redundancy: 1.9 % / Rmerge(I) obs: 0.4818 / Mean I/σ(I) obs: 0.69 / Num. unique obs: 3285 / CC1/2: 0.591 / CC star: 0.862 / Rpim(I) all: 0.4818 / Rrim(I) all: 0.6814 / % possible all: 74.25

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Processing

Software
NameVersionClassification
SERGUIdata collection
XDSdata reduction
XSCALEdata scaling
PHENIX1.20.1-4487phasing
Cootmodel building
PHENIX1.19.2_4158refinement
RefinementMethod to determine structure: MOLECULAR REPLACEMENT / Resolution: 2.8→19.87 Å / SU ML: 0.3948 / Cross valid method: FREE R-VALUE / σ(F): 0.01 / Phase error: 27.1523
Stereochemistry target values: GeoStd + Monomer Library + CDL v1.2
RfactorNum. reflection% reflection
Rfree0.2529 1860 4.78 %
Rwork0.2107 37075 -
obs0.2128 38941 86.55 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.1 Å / Solvent model: FLAT BULK SOLVENT MODEL
Displacement parametersBiso mean: 51.17 Å2
Refinement stepCycle: LAST / Resolution: 2.8→19.87 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms11215 0 0 21 11236
Refine LS restraints
Refine-IDTypeDev idealNumber
X-RAY DIFFRACTIONf_bond_d0.00211494
X-RAY DIFFRACTIONf_angle_d0.473115645
X-RAY DIFFRACTIONf_chiral_restr0.04261725
X-RAY DIFFRACTIONf_plane_restr0.00382023
X-RAY DIFFRACTIONf_dihedral_angle_d10.77234175
LS refinement shell
Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkRefine-ID% reflection obs (%)
2.8-2.870.38321200.31052537X-RAY DIFFRACTION74.2
2.87-2.960.3241300.29152453X-RAY DIFFRACTION76.69
2.96-3.050.35071270.27522598X-RAY DIFFRACTION78.76
3.05-3.160.3171200.2732507X-RAY DIFFRACTION75.97
3.16-3.290.33421410.25452902X-RAY DIFFRACTION87.49
3.29-3.440.271520.24132962X-RAY DIFFRACTION89.46
3.44-3.620.30351500.21282973X-RAY DIFFRACTION90.6
3.62-3.840.26031570.212969X-RAY DIFFRACTION91.75
3.84-4.140.22261500.19522995X-RAY DIFFRACTION91.13
4.14-4.550.23511410.17462969X-RAY DIFFRACTION89.19
4.55-5.20.21351560.16343025X-RAY DIFFRACTION92.31
5.2-6.510.21671620.19613147X-RAY DIFFRACTION95.39
6.51-19.870.1911540.19143038X-RAY DIFFRACTION92.55
Refinement TLS params.

Method: refined / Refine-ID: X-RAY DIFFRACTION

IDL112)L122)L132)L222)L232)L332)S11 (Å °)S12 (Å °)S13 (Å °)S21 (Å °)S22 (Å °)S23 (Å °)S31 (Å °)S32 (Å °)S33 (Å °)T112)T122)T132)T222)T232)T332)Origin x (Å)Origin y (Å)Origin z (Å)
12.810500052210.2220392424180.1462388438834.24648716302-1.20759173613.89253136154-0.205551262354-0.3550999738890.2849512627391.06908609031-0.128304733868-0.260132163195-1.35443508004-0.545295992138-0.2682343764620.2981988753440.1112860435310.01165329536670.41719401803-0.03922524245680.346966565302-30.071541619912.3724969103-2.65007836176
23.711323802540.833988438949-0.7530839178374.049340028-0.3399736561013.36572922907-0.146461321415-0.278079673449-0.5539399974870.3247944908440.1251703345940.1276330636330.284771447149-0.1417396393410.005750910350110.3208795373130.05477526629310.01006665381220.3605597725570.06772593299470.35075046181-32.7994182484-8.72383306126-4.51444945715
35.541409471610.127810807618-0.5929114976243.99737041483-0.05889491712624.58993232281-0.0342888980018-0.3722629046860.07370053051780.5074257582140.06782274919440.2229367254870.148514206767-0.417337083837-0.005069352743950.3848830904310.007813810251790.0394877580170.2927288086550.06495413067150.382151895141-36.220459811-2.99801890647-1.71173517664
45.768346587910.9729100252520.1413364393593.941054789951.123041137995.242485342580.144035176716-0.2164593632810.203796191062-0.218771025135-0.267712926571-0.260854580630.4919421619110.0936968495504-0.1501444990670.3693432518990.02494587179480.008015191676420.2590115161970.1122344195680.282876063956-22.3912978722-4.28045341597-8.95771567928
50.09311073818160.162900296367-0.1192297514813.51751913227-2.233332379612.032500319390.2100297815520.2098459036870.208587851355-0.1070656854980.001464216767950.478564834257-0.535258704304-0.902506925928-0.4242337513290.4638716610940.0944162666835-0.0262914862910.4003062250090.03057096344550.617831466193-32.642943019614.5535649286-14.8359489793
62.394341076810.400727644574-0.2695434522740.8293015421790.3218862610032.98400197669-0.00322236158891-0.08825048385740.38075688085-0.0874542124585-0.0851073303415-0.0696514186113-0.3449584557070.01895528403590.08255918579810.3760354168230.0588244899673-0.03069070548150.2481408779870.08395137047620.478813562865-20.103982126714.3708277256-15.2348710174
73.439709188491.232004448810.6601627374371.943992713930.5396080691042.898551483790.03110267237250.1565020753380.00240003283317-0.167776448205-0.2516227996980.02901579821680.254729120766-0.1092719531090.1740632003110.2725619064040.07276463581980.01547402588670.3881076163560.01326178113730.50253669095-28.7307574227-63.124460489320.9662687669
81.74896717742-0.7734756724811.864157465873.143854862990.3795391652976.19121019801-0.03490245773380.2513959230110.135269221492-0.471881824475-0.1233304785230.505542467822-0.204522121987-0.4432265143670.1429376651930.3555636208460.0765489824544-0.05301124009640.4519073485110.05240944847980.446890894888-40.6576819872-49.024884359918.6462756536
94.01826519954-0.158492666881-1.407948065224.850670522570.019385977596.287723569520.1426904953820.1624908701810.492772977283-0.262951100682-0.0415771577757-0.409950621482-0.002814059973430.13392409319-0.07620314655510.3106698081030.0778848126836-0.02575670631990.2769538581520.07915103978310.36841338137-25.2781855471-50.683861414223.4875521799
103.06998811305-0.1351283552670.7246591895332.48314008627-0.1961465103853.278993775960.02456145912690.0195762894428-0.5051115957960.0928017227171-0.08951049670020.2598321824360.357345504588-0.1846828638470.1045362258330.326212991103-0.02756501234460.02997316018830.2877912580760.03357963113060.512973628425-23.2049239333-69.644241731232.028110005
112.548639257140.2600833855343.940820107862.946797202383.442971150758.437140362960.1435441829670.270244164993-0.145911851990.5868805564660.04934629034710.6191220687530.9434943706580.653692642924-0.3803675307470.4940378847820.02677018697320.1211694510480.3556968125470.1786373854060.639114153954-6.7735015268-24.5654073938-27.5155888147
121.713776642850.698288632441-0.05349651936922.16959902490.3908431213712.190561403850.01922210380190.222574461314-0.100714970181-0.192724383139-0.03082213744040.05331249953970.09396755641110.07135880912180.08112578073920.3681905559280.0618145397035-0.00700681390340.3195251324760.140287311850.489336058233-11.7506838388-14.1985166408-24.7687070635
131.72112465941-0.02271409389610.2634953350533.882701483912.320940320632.959046353570.0284158232561-0.05214122276960.08646204717550.5899815742860.217657101413-0.3743087494340.2482235763590.250802278925-0.1500394667810.2908432431790.03148677764540.03719133503170.2440928875550.1143258868890.394030551703-5.73131267801-12.3030568593-26.9958238256
143.72817140185-0.300423034954-0.5787883610111.461903141310.2499374367280.9448045912430.164926624457-0.32995395917-0.4355879568440.0674031858184-0.133796081125-0.1174935900480.1281788486930.221299789898-0.05578384412190.4200724686270.04126389140960.003637685104670.2661047038050.1013895470270.46990650322614.3635155009-35.307760331-36.6565825907
152.47192720256-1.71764861016-0.7247614713672.767554564031.455699706910.8939575892150.06855479680950.7512232826560.637175735613-0.6586322691080.2132149617610.11238951132-0.3349837042830.0498264490987-0.2595134936040.5067063416240.193075430884-0.2631781421810.1625817514060.1988593399860.966775202292-6.84389826682-30.627285161844.574742748
164.49036458565-0.21739486873-0.07529122168544.237795143180.8644645890613.15924021967-0.0905651290425-0.05317726821380.2632418967860.114045159311-0.09084724344020.264938001130.0194403590135-0.109922191930.2276667815040.2922497807420.00789444789884-0.03030594025870.2826966709890.09758389527560.379692281965-9.94665078212-42.522197079741.4245569112
172.02357221142-0.9675515036140.8594731075292.778899027130.1146983885570.825959198534-0.1505990521730.01422442407640.138915299307-0.0248703370018-0.005591642399540.260421456840.0746939178146-0.0006612869547180.2077177863910.2441521774140.01223577341470.03322196842130.3417127909910.06458760784290.527330445939-11.5333384007-41.469754477743.4520590573
181.283767030131.314481826150.1763598068671.759112215720.5786470594221.060880321860.0736049737643-0.08676433923790.2295500600850.1348174040360.0711235575642-0.335933156514-0.1275106683420.118721989707-0.07674444999230.4418999631330.123401378619-0.08929636459290.431582244845-0.07265407119450.95156697205810.9029114014-24.1594412953.8017144801
195.27482349321-0.53451961579-0.4703708304680.5630037921621.24287652022.0378957014-0.06997178621270.7951345777121.30592980522-0.3737711854190.116461261235-0.384303439499-0.3894584816250.544856088731-0.04357412630340.5180898838850.0003148806241980.001725266896120.5682732927890.2050642166161.1212440671215.1208363007-15.939936173548.3673425797
201.61215922674-0.869011691911-0.1439038512190.545797186657-0.6978095191312.549189111110.01451358709560.1074718347450.0999692557173-0.575946514216-0.0145372639950.0459425293567-0.4786217892550.0848776281377-0.1089157384180.706630949607-0.03400269399110.07600496201420.3654471269570.1550045130980.5563090076998.28890093886-1.43934500435-40.6069921011
215.80631689305-2.238437904993.756311694723.21323239954-0.1926909014923.92672371480.01122502511340.7451951460960.346630310922-0.7637819122120.08471576111510.105272606531-0.374914384827-0.0221519846204-0.1117274129760.6146107292720.01008561393930.03674223591860.3276027841480.2058848435730.532750744009-0.7802165569375.28134159125-38.1980634271
223.91032238371-1.93518008461-0.6395518604431.553890335091.627777725453.548586766620.0742633026764-0.06171966415080.191521555423-0.1682715223810.142522065454-0.330711235737-0.220312503530.314237278717-0.1950373011140.343713532315-0.001455493108590.04132046645560.2518368320290.07279505193950.4539078616946.96903968329-0.793059586156-29.9061249721
233.278543662550.822967488377-1.025453858341.0398972899-0.4236394774341.34568466164-0.06958172015260.6917624692130.347778573871-0.248191810570.0576206147471-0.151166555709-0.0372972787732-0.3003096638-0.08190272768510.406675884467-0.02056103037450.01232261659670.3235965690640.09944716414210.4311701439096.93936153301-6.50868422006-38.0243300961
243.16948675465-0.07407311868640.9331830968394.42890850133.303275969432.903996326870.1471551934180.139988747735-0.315021798381-0.140547573129-0.1822198281680.0100918276561-0.07945743556830.227871856560.01276401633910.2350857263520.0307068646842-0.008265318500850.2771340728790.06491964955670.46149844263519.4308494684-32.149536486-48.4890917144
252.696545156370.786803408888-0.09789641036851.735073679830.7426210387340.572527076440.3060863627890.0261527263507-0.107207001394-0.0292473681263-0.00185820267537-0.281369896588-0.1072568397810.134311790504-0.1779297065440.4182495638880.03702690684790.004763887115860.3601140167570.1240710096240.40263999646417.3579001648-25.0099417664-48.0650596121
264.187705014311.927221407910.2440158238213.961842112361.584865218832.14706034939-0.2749246457910.369062329239-0.659331275253-0.663484641150.252604621889-0.262905843774-0.004072397035340.0729566229171-0.007714432546110.4279815719420.06212936076820.05264387122010.3648689316990.06559809229820.50580558436121.6860523784-34.1448396272-54.0466867838
272.443324965771.37250422202-1.168736746482.39233102772-0.9663359877733.63569453481-0.05737788116180.0960111448885-0.1538866746840.6841328140910.08803172610570.002257474195030.572166945236-0.0118130957183-0.01330619755280.6048218733350.162052770144-0.0939901774020.3053172094860.1217336725310.4132155186976.08042439952-53.988616115857.523323173
282.487276404971.195311241871.40071884761.272121135310.442655146523.541640915990.0436969093520.119071847053-0.05350787618960.05863859647490.125471185928-0.1924158171890.2243752466050.349167505445-0.2176834325560.384230532550.118860589911-0.02645601215810.2948108565930.0364456389270.4802626789235.70289794763-55.367872196148.112679891
291.91939246164-0.640266253196-1.27721045222.72841875979-0.1684340948741.681398627660.143895126389-0.643238678371-0.08519382397950.5944306262170.228387204975-0.4602465043770.245221710204-0.0617792374591-0.1117942297660.5112417299630.13503808913-0.06884296590630.3532350364190.06719858720840.4086043897316.8704694862-48.895677158755.0065550752
302.098269620722.603842047450.09920956960094.246035547391.04448340332.220372191910.110178857847-0.1267640008410.3325047390190.605209722917-0.0534182726875-0.1879883173850.006661435240890.183321610601-0.118319875980.5582051435430.139601184944-0.2155564780540.652422345997-0.1276019157280.82256222433819.1055693147-23.340974636465.8570699628
310.506850687378-1.22052451994-0.307069460065.31728265061.473086289982.842824247160.132999460581-0.132656955235-0.02905518581810.336088409261-0.215899358743-0.4666614841120.0673405312733-0.3242939614270.08050843365310.3920314085560.079051446489-0.1476149200240.6065609919090.05376344968850.63433387129517.3393103995-30.996193972464.901537148
320.123186066581-0.513474120665-0.5502281048895.238968465782.584713171482.04383684395-0.1830512212390.149542645155-0.06946072145541.150626599080.0973539838788-0.1822051963350.1179902735120.3211201243340.05255794027210.7762368032130.0907362540636-0.3376769178070.65560244626-0.164248121911.0656414922921.4029846297-20.571642576872.322947163
Refinement TLS group

Refine-ID: X-RAY DIFFRACTION

IDRefine TLS-IDSelection detailsAuth asym-IDLabel asym-IDAuth seq-IDLabel seq-ID
11chain 'A' and (resid 108 through 144 )AA108 - 1441 - 37
22chain 'A' and (resid 145 through 201 )AA145 - 20138 - 91
33chain 'A' and (resid 202 through 264 )AA202 - 26492 - 154
44chain 'A' and (resid 265 through 290 )AA265 - 290155 - 173
55chain 'A' and (resid 291 through 316 )AA291 - 316174 - 199
66chain 'A' and (resid 317 through 438 )AA317 - 438200 - 285
77chain 'B' and (resid 108 through 163 )BB108 - 1631 - 56
88chain 'B' and (resid 164 through 237 )BB164 - 23757 - 126
99chain 'B' and (resid 238 through 290 )BB238 - 290127 - 170
1010chain 'B' and (resid 291 through 438 )BB291 - 438171 - 283
1111chain 'H' and (resid 2 through 18 )HC2 - 181 - 17
1212chain 'H' and (resid 19 through 83 )HC19 - 8318 - 82
1313chain 'H' and (resid 84 through 118 )HC84 - 11883 - 117
1414chain 'H' and (resid 119 through 223 )HC119 - 223118 - 222
1515chain 'I' and (resid 2 through 18 )ID2 - 181 - 17
1616chain 'I' and (resid 19 through 60 )ID19 - 6018 - 59
1717chain 'I' and (resid 61 through 108 )ID61 - 10860 - 107
1818chain 'I' and (resid 109 through 197 )ID109 - 197108 - 192
1919chain 'I' and (resid 198 through 222 )ID198 - 222193 - 217
2020chain 'L' and (resid 1 through 18 )LE1 - 181 - 18
2121chain 'L' and (resid 19 through 30 )LE19 - 3019 - 30
2222chain 'L' and (resid 31 through 91 )LE31 - 9131 - 91
2323chain 'L' and (resid 92 through 114 )LE92 - 11492 - 114
2424chain 'L' and (resid 115 through 151 )LE115 - 151115 - 151
2525chain 'L' and (resid 152 through 173 )LE152 - 173152 - 173
2626chain 'L' and (resid 174 through 214 )LE174 - 214174 - 214
2727chain 'M' and (resid -1 through 18 )MF-1 - 181 - 20
2828chain 'M' and (resid 19 through 91 )MF19 - 9121 - 93
2929chain 'M' and (resid 92 through 114 )MF92 - 11494 - 116
3030chain 'M' and (resid 115 through 151 )MF115 - 151117 - 153
3131chain 'M' and (resid 152 through 175 )MF152 - 175154 - 177
3232chain 'M' and (resid 176 through 214 )MF176 - 214178 - 216

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