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- PDB-9lgg: Crystal structure of the human MuSK(Ig3_Fz)/L1 peptide complex -

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Basic information

Entry
Database: PDB / ID: 9lgg
TitleCrystal structure of the human MuSK(Ig3_Fz)/L1 peptide complex
ComponentsMuscle, skeletal receptor tyrosine-protein kinase,Ig3-Fz domains of hMuSK:L1 peptide
KeywordsMEMBRANE PROTEIN / muscle-specific receptor tyrosine kinase / MuSK / neuromuscular junction / RaPID peptide
Function / homology
Function and homology information


positive regulation of protein geranylgeranylation / regulation of synaptic assembly at neuromuscular junction / skeletal muscle acetylcholine-gated channel clustering / Wnt-protein binding / neuromuscular junction development / ECM proteoglycans / transmembrane receptor protein tyrosine kinase activity / cell surface receptor protein tyrosine kinase signaling pathway / neuromuscular junction / receptor protein-tyrosine kinase ...positive regulation of protein geranylgeranylation / regulation of synaptic assembly at neuromuscular junction / skeletal muscle acetylcholine-gated channel clustering / Wnt-protein binding / neuromuscular junction development / ECM proteoglycans / transmembrane receptor protein tyrosine kinase activity / cell surface receptor protein tyrosine kinase signaling pathway / neuromuscular junction / receptor protein-tyrosine kinase / memory / positive regulation of protein phosphorylation / protein autophosphorylation / protein tyrosine kinase activity / postsynaptic membrane / cell differentiation / receptor complex / positive regulation of gene expression / ATP binding / metal ion binding / plasma membrane
Similarity search - Function
Frizzled domain / Frizzled cysteine-rich domain superfamily / Fz domain / Frizzled (fz) domain profile. / Immunoglobulin domain / Immunoglobulin I-set / Immunoglobulin I-set domain / : / Immunoglobulin subtype 2 / Immunoglobulin C-2 Type ...Frizzled domain / Frizzled cysteine-rich domain superfamily / Fz domain / Frizzled (fz) domain profile. / Immunoglobulin domain / Immunoglobulin I-set / Immunoglobulin I-set domain / : / Immunoglobulin subtype 2 / Immunoglobulin C-2 Type / Tyrosine-protein kinase, catalytic domain / Tyrosine kinase, catalytic domain / Tyrosine protein kinases specific active-site signature. / Immunoglobulin subtype / Immunoglobulin / Tyrosine-protein kinase, active site / Serine-threonine/tyrosine-protein kinase, catalytic domain / Protein tyrosine and serine/threonine kinase / Ig-like domain profile. / Immunoglobulin-like domain / Immunoglobulin-like domain superfamily / Protein kinase, ATP binding site / Protein kinases ATP-binding region signature. / Immunoglobulin-like fold / Protein kinase domain profile. / Protein kinase domain / Protein kinase-like domain superfamily
Similarity search - Domain/homology
Muscle, skeletal receptor tyrosine-protein kinase
Similarity search - Component
Biological speciesHomo sapiens (human)
synthetic construct (others)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.69 Å
AuthorsMatoba, K. / Mizutani, F. / Arimori, T. / Takagi, J.
Funding support Japan, 1items
OrganizationGrant numberCountry
Japan Agency for Medical Research and Development (AMED) Japan
CitationJournal: Structure
Title: Muscle-specific tyrosine kinase activation by a peptide-based dimerizer is orientation dependent
Authors: Mizutani, F. / Matoba, K. / Peacock, H. / Yamada, M. / Mihara, E. / Higuchi, O. / Suga, H. / Arimori, T. / Takagi, J.
History
DepositionJan 10, 2025Deposition site: PDBJ / Processing site: PDBJ
Revision 1.0Dec 3, 2025Provider: repository / Type: Initial release

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Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

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Assembly

Deposited unit
A: Muscle, skeletal receptor tyrosine-protein kinase,Ig3-Fz domains of hMuSK:L1 peptide
B: Muscle, skeletal receptor tyrosine-protein kinase,Ig3-Fz domains of hMuSK:L1 peptide
C: Muscle, skeletal receptor tyrosine-protein kinase,Ig3-Fz domains of hMuSK:L1 peptide
D: Muscle, skeletal receptor tyrosine-protein kinase,Ig3-Fz domains of hMuSK:L1 peptide
hetero molecules


Theoretical massNumber of molelcules
Total (without water)126,6709
Polymers124,7514
Non-polymers1,9195
Water00
1
A: Muscle, skeletal receptor tyrosine-protein kinase,Ig3-Fz domains of hMuSK:L1 peptide
B: Muscle, skeletal receptor tyrosine-protein kinase,Ig3-Fz domains of hMuSK:L1 peptide
C: Muscle, skeletal receptor tyrosine-protein kinase,Ig3-Fz domains of hMuSK:L1 peptide
D: Muscle, skeletal receptor tyrosine-protein kinase,Ig3-Fz domains of hMuSK:L1 peptide
hetero molecules

A: Muscle, skeletal receptor tyrosine-protein kinase,Ig3-Fz domains of hMuSK:L1 peptide
B: Muscle, skeletal receptor tyrosine-protein kinase,Ig3-Fz domains of hMuSK:L1 peptide
C: Muscle, skeletal receptor tyrosine-protein kinase,Ig3-Fz domains of hMuSK:L1 peptide
D: Muscle, skeletal receptor tyrosine-protein kinase,Ig3-Fz domains of hMuSK:L1 peptide
hetero molecules


Theoretical massNumber of molelcules
Total (without water)253,34018
Polymers249,5028
Non-polymers3,83810
Water0
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
crystal symmetry operation4_455-x-1,-y,z1
Buried area30110 Å2
ΔGint-88 kcal/mol
Surface area102370 Å2
MethodPISA
Unit cell
Length a, b, c (Å)103.644, 103.644, 305.216
Angle α, β, γ (deg.)90.000, 90.000, 120.000
Int Tables number172
Space group name H-MP64
Space group name HallP64
Symmetry operation#1: x,y,z
#2: x-y,x,z+2/3
#3: y,-x+y,z+1/3
#4: -y,x-y,z+1/3
#5: -x+y,-x,z+2/3
#6: -x,-y,z

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Components

#1: Protein
Muscle, skeletal receptor tyrosine-protein kinase,Ig3-Fz domains of hMuSK:L1 peptide / Muscle-specific tyrosine-protein kinase receptor / MuSK / L1 peptide


Mass: 31187.795 Da / Num. of mol.: 4
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human), (gene. exp.) synthetic construct (others)
Gene: MUSK / Production host: Homo sapiens (human)
References: UniProt: O15146, receptor protein-tyrosine kinase
#2: Polysaccharide
2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose


Type: oligosaccharide / Mass: 424.401 Da / Num. of mol.: 4
Source method: isolated from a genetically manipulated source
DescriptorTypeProgram
DGlcpNAcb1-4DGlcpNAcb1-Glycam Condensed SequenceGMML 1.0
WURCS=2.0/1,2,1/[a2122h-1b_1-5_2*NCC/3=O]/1-1/a4-b1WURCSPDB2Glycan 1.1.0
[]{[(4+1)][b-D-GlcpNAc]{[(4+1)][b-D-GlcpNAc]{}}}LINUCSPDB-CARE
#3: Sugar ChemComp-NAG / 2-acetamido-2-deoxy-beta-D-glucopyranose / N-acetyl-beta-D-glucosamine / 2-acetamido-2-deoxy-beta-D-glucose / 2-acetamido-2-deoxy-D-glucose / 2-acetamido-2-deoxy-glucose / N-ACETYL-D-GLUCOSAMINE


Type: D-saccharide, beta linking / Mass: 221.208 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C8H15NO6
IdentifierTypeProgram
DGlcpNAcbCONDENSED IUPAC CARBOHYDRATE SYMBOLGMML 1.0
N-acetyl-b-D-glucopyranosamineCOMMON NAMEGMML 1.0
b-D-GlcpNAcIUPAC CARBOHYDRATE SYMBOLPDB-CARE 1.0
GlcNAcSNFG CARBOHYDRATE SYMBOLGMML 1.0
Has ligand of interestN
Has protein modificationY

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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: 3.79 Å3/Da / Density % sol: 67.58 %
Crystal growTemperature: 293 K / Method: vapor diffusion, hanging drop
Details: 0.1M Na-Acetate(pH 6.0), 0.2M NaCl, 7% PEG 8000, 10% Glycerol

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Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: SPring-8 / Beamline: BL44XU / Wavelength: 0.999 Å
DetectorType: DECTRIS EIGER X 16M / Detector: PIXEL / Date: Oct 2, 2021
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.999 Å / Relative weight: 1
ReflectionResolution: 2.69→49.07 Å / Num. obs: 50770 / % possible obs: 99.4 % / Redundancy: 4.51 % / Biso Wilson estimate: 72.51 Å2 / CC1/2: 0.997 / Rsym value: 0.1 / Net I/σ(I): 10.38
Reflection shellResolution: 2.69→2.86 Å / Mean I/σ(I) obs: 1.38 / Num. unique obs: 8124 / CC1/2: 0.673 / Rsym value: 1.096 / % possible all: 98.5

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Processing

Software
NameVersionClassification
PHENIX1.19.2_4158refinement
XDSdata reduction
XDSdata scaling
PHASERphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT / Resolution: 2.69→38.68 Å / SU ML: 0.4441 / Cross valid method: FREE R-VALUE / σ(F): 1.34 / Phase error: 27.2658
Stereochemistry target values: GeoStd + Monomer Library + CDL v1.2
RfactorNum. reflection% reflection
Rfree0.2425 2535 5 %
Rwork0.2039 48185 -
obs0.2059 50720 99.33 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL
Displacement parametersBiso mean: 77.14 Å2
Refinement stepCycle: LAST / Resolution: 2.69→38.68 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms7923 0 126 0 8049
Refine LS restraints
Refine-IDTypeDev idealNumber
X-RAY DIFFRACTIONf_bond_d0.0048243
X-RAY DIFFRACTIONf_angle_d0.636111219
X-RAY DIFFRACTIONf_chiral_restr0.04281310
X-RAY DIFFRACTIONf_plane_restr0.00581417
X-RAY DIFFRACTIONf_dihedral_angle_d4.87971125
LS refinement shell
Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkRefine-ID% reflection obs (%)
2.69-2.750.4581350.43952570X-RAY DIFFRACTION95.82
2.75-2.80.37411440.38092739X-RAY DIFFRACTION99.79
2.8-2.860.33531380.31382638X-RAY DIFFRACTION99.5
2.86-2.930.33031400.2742666X-RAY DIFFRACTION99.61
2.93-30.32551410.26962676X-RAY DIFFRACTION99.72
3-3.080.31961420.26362692X-RAY DIFFRACTION99.65
3.08-3.170.30681410.26742668X-RAY DIFFRACTION99.68
3.17-3.280.33781410.28292694X-RAY DIFFRACTION99.65
3.28-3.390.30351420.2682700X-RAY DIFFRACTION99.65
3.39-3.530.26631400.21272665X-RAY DIFFRACTION99.82
3.53-3.690.27031430.21062708X-RAY DIFFRACTION99.65
3.69-3.880.2441390.19372656X-RAY DIFFRACTION99.64
3.88-4.130.22211420.18222685X-RAY DIFFRACTION99.54
4.13-4.440.18661410.15892687X-RAY DIFFRACTION99.68
4.45-4.890.17421420.15042699X-RAY DIFFRACTION99.65
4.89-5.60.21311420.1672682X-RAY DIFFRACTION99.58
5.6-7.040.22831410.192687X-RAY DIFFRACTION99.37
7.05-38.680.20311410.17852673X-RAY DIFFRACTION97.98
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)
14.283761629470.218249562999-3.517422529043.61562781858-0.02938185100959.04337538651-0.0026265032525-0.3937479378-0.08990569080940.2192689694180.0135242512969-0.1315717933380.2904530742420.0322961138534-0.01535221717090.522580884955-0.118011898018-0.06486826834630.3773528751380.03761806134380.454134274732-62.0342985536-45.2204194683-11.407751427
27.1396338886-2.992213615730.8488869283539.290420351-2.685869510959.04104113439-0.2487275222840.512619753153-0.780267895146-0.6522186247280.479783511670.6774878831260.842430716504-0.935627327975-0.2357206500970.847714117128-0.2254121637520.06094285929680.566657132990.01781600661220.521184878364-62.9367037811-44.1966984029-42.8630909379
35.083032211250.1682967493741.64939936295.78174025035-4.603026375054.49869272091-0.377525834422-0.1146575332690.1613746703-0.03572876241670.3482825293080.523407262041-0.404742648671-1.403317857340.02804382467740.68604511659-0.007566148413930.0148772261320.5713646815870.1188346282560.472687538895-64.7069846744-31.3925522996-36.6159550795
43.52700500284-0.0793089477595-2.580967430774.9121430669-2.782077534216.43566192197-0.06694126822310.1844154672630.276720601164-0.223779991654-0.102109035919-0.46816858317-0.2225356772870.5437587957880.1136935630530.678378475987-0.13158331970.03972240406530.5306470200020.1264571336850.575243684254-56.0578080785-28.6001796956-44.0142133552
54.49467860135-2.8702469983-4.017952187361.764626984922.391135165183.564631186730.2430913805540.459323839964-0.602642778169-0.793588255415-0.5528176158210.239087810992-0.525180866703-0.03653229105630.5525787955820.846108381071-0.0422852795345-0.03414519782740.648452436065-0.02990256512420.572992465311-75.4374615873-22.926966091-42.4126866007
62.618164481393.978434706960.7817534774046.293250324350.6499994379325.262450020270.239670958095-0.217303940144-1.770688925611.49481310844-0.4018682330750.6971103710450.9406365918660.09970326491060.1745017146270.858874300921-0.0567738434065-0.0502646718140.359379895304-0.04639810163520.990600201827-91.9567939729-30.7614110312-24.6036603958
71.599376190550.2167459133380.2938347877082.45347639778-0.1261824700256.791546820840.05836298222010.2536325739380.0277881433003-0.2714624387830.1005723871040.2539803512990.285146900016-0.828912105892-0.1733021057150.500386491282-0.089614188325-0.08131098690350.4742462826690.06281704385930.572289605133-91.5007165146-21.1643069981-33.0717882775
87.99427802798-3.179312517864.527718439526.36833581933-0.3196798954645.54179376577-0.1498979339750.610146383984-0.341225717446-0.1539276375320.246909138542-0.2677184204750.3339877402880.754310981258-0.04682788594230.547779541929-0.09076570575120.01394589479920.518516425527-0.1046720098630.559438094564-74.1077580299-20.3441436178-15.1192845047
96.70110553822-2.251410145731.196775360675.019641225121.409243719656.89125680327-0.2688607345410.343217864990.7478793595590.3021414266090.122911596459-0.191312150738-1.328565260130.492951246290.03209421680720.82582900878-0.143562842949-0.1038509167110.4032315923210.07475687394960.545308144226-78.6481812552-11.8927104246-11.8985058449
105.12231187082-7.28088348188-5.33506221979.719967466847.938745414425.96167093259-0.477806124233-0.7488813305560.4615952551980.5979103342320.872008374789-0.6248863859940.2051208270650.725394475401-0.3857011298080.877830956946-0.128449614994-0.05254194456310.5332706629040.005696774730250.634953493737-72.4156406424-21.7972331119-7.09430596599
118.133847563234.169165209821.306168808812.387540395621.19900825662.03941996344-1.076490133070.793877910896-0.830002644716-1.743141911370.6088965626380.5377129889520.435312215851-0.3568063930730.5014814577220.81481804077-0.2242532565410.04966092037090.656028244286-0.04281344879180.593562660445-71.8063455337-47.3707113961-30.5322275196
123.100863319344.05237323970.1240737253777.577953787990.6474737924531.132449153290.095409102103-0.460594165255-0.1110445675050.160150783785-0.142889205628-0.604693734849-0.09950659289080.0739003839810.0274802971870.349497568777-0.020203916932-0.08134024308820.445868313446-0.001246665265370.45530596383-33.3951659626-4.7961385829615.2313661452
135.388543987730.02614126663241.887688918936.05130650277-0.4100770744066.24970080037-0.2827778107680.527491933320.108332814874-1.071134159130.1341997576580.179042010812-0.02017794010130.2524682419970.1957836601070.492176432776-0.106697668128-0.04120828784250.4370727142630.0169871944140.38827652715-50.4870551209-19.37042347421.0747512767
140.591559535729-1.89828168396-0.4309622655163.595854642721.43003136120.3988190943080.03497194575830.108391013344-0.2096448256850.215165243007-0.1726179186180.3584287417050.279663455561-0.2085761606340.2191134072980.605215486989-0.1676282290440.0864766585410.5372351877220.09680546214780.633495750349-61.4784068718-5.1128630833210.545892397
157.338150330374.71893924074-3.237006098833.84213278205-1.479405946193.14598360820.154787396925-0.4414142593940.338767305084-0.10681548479-0.09842071799340.3118354875930.02165269658970.320989662369-0.04825544246270.679961779407-0.0542456739707-0.1867823704590.4386632054330.1262614005230.513158719536-56.752239929722.6602424636-70.7554134475
164.569998122244.472454185531.064204784285.192199110981.225530360740.290736516225-0.683339427213-0.822644691122-0.243383303639-0.003807136071570.298442824626-0.4850869291240.6351305246080.3453898354410.4731990476731.05155702370.0908834693068-0.1597426911790.3495724012140.2003905948050.428513550286-61.909613309417.6090500474-69.3153709336
175.548424056640.124879541503-1.536256484923.20680124138-0.4979635040536.9939023022-0.554409913940.1583061182680.4860520133280.07758139711340.292956212589-0.689165384449-0.1149690774460.8164669992860.3084538179540.718191742273-0.0846195942341-0.1204687079680.512639806896-0.005862091001130.686750442773-50.068957701228.2135848378-65.070611237
184.673801785095.73472475734-2.131321472337.04495966771-2.340196390563.70225409125-0.446319690379-1.194452018561.75283407095-0.2010581924350.06611030647660.343685375209-0.25917792180.5922829834410.4442057546740.811521979352-0.0851287402946-0.1335909834530.583428226512-0.1756094141350.562610224485-58.493018576728.6606588891-65.6480226504
196.943343490740.9099811960311.062200097096.713998397420.2939808822245.971430448460.7445870199880.0417398632441-1.5161382187-1.1041305091-0.381208822170.1197948159611.09528166766-0.0302119354952-0.292206797760.84323327643-0.0490904641769-0.0008748003542860.476886609170.1654208973380.59210654624-74.1749987496-2.15001850658-70.6655776914
205.70917556791.7942826507-0.2250712801735.20730951465-0.2956620878345.275460537450.342809271518-0.105649856228-0.268909211013-0.467719606201-0.487148030623-0.6077088820040.401291197384-0.1670098113410.06360237190960.871411943709-0.0633300717843-0.1495222028220.4861803796990.2849769093470.624286359485-71.05831158070.476861695908-65.9891048691
212.91271617930.62718229747-0.3064505524776.97008123964-0.6566357899464.863684763370.212261347848-0.129061207854-1.60844959245-0.1320683021830.10333519976-0.7371918780040.02330201778040.244373032816-0.2092395857160.675107914288-0.0465376904609-0.1085227074480.6916116100530.3425463939660.8749389365-63.7441827567-6.9937531911-57.0164870335
224.53937962029-1.21606817974-0.7795885903615.23767893633-2.636260713173.11296783159-0.0339735118763-0.264213598571-1.327865113650.985788536346-0.06267012018790.1971513526910.123780694632-0.16661415777-0.1346168519550.863078453772-0.223170015565-0.01611078458320.6221791702740.193044390450.75547840396-78.2777293857-7.39766493184-57.6691224723
232.51369154868-2.44367113058-0.6567050860513.35111756832-0.2391883926832.57654596274-0.374149608296-1.10536775815-0.2595895639170.7938662846370.0774737523988-0.4195327484990.0411987978581-0.110336372050.3119790403391.10800569982-0.119607422609-0.07668322272260.9011477286670.2582677937570.649707493303-71.8530990286-3.34380319128-50.2609062859
246.01043317072-4.34301682815-0.7199304771543.476309585110.1543233072760.300014396390.00181952172871-1.41995645436-0.454404596058-0.4546375244280.490905819920.1497926183120.348532667140.0802710865797-0.5249050556560.998530455303-0.2545909058950.0381527427210.858709510324-0.06787963519370.484439185628-56.676717272-13.4846586535-60.0503567977
252.76472280645-0.26626640521-4.871425809612.152879723340.8707408037318.646087426070.02542370184330.625549376680.164830230575-1.48103293905-0.2996687680621.10351578639-0.2997832220760.1011142884070.4081489015660.9856142608520.0993873669204-0.04182009880360.759321390761-0.1591993184210.803550597753-41.4345658261-4.62139074123-76.3950395866
Refinement TLS group

Refine-ID: X-RAY DIFFRACTION

IDRefine TLS-IDSelection detailsAuth asym-IDLabel asym-IDAuth seq-IDLabel seq-ID
11chain 'A' and (resid 210 through 304 )AA210 - 3041 - 95
22chain 'A' and (resid 305 through 343 )AA305 - 34396 - 127
33chain 'A' and (resid 344 through 378 )AA344 - 378128 - 162
44chain 'A' and (resid 379 through 446 )AA379 - 446163 - 223
55chain 'A' and (resid 447 through 464 )AA447 - 464224 - 241
66chain 'A' and (resid 465 through 478 )AA465 - 478242 - 255
77chain 'B' and (resid 210 through 359 )BB210 - 3591 - 143
88chain 'B' and (resid 360 through 378 )BB360 - 378144 - 162
99chain 'B' and (resid 379 through 436 )BB379 - 436163 - 212
1010chain 'B' and (resid 437 through 464 )BB437 - 464213 - 240
1111chain 'B' and (resid 465 through 478 )BB465 - 478241 - 254
1212chain 'C' and (resid 209 through 343 )CC209 - 3431 - 128
1313chain 'C' and (resid 344 through 443 )CC344 - 443129 - 221
1414chain 'C' and (resid 444 through 475 )CC444 - 475222 - 253
1515chain 'D' and (resid 210 through 264 )DD210 - 2641 - 55
1616chain 'D' and (resid 265 through 277 )DD265 - 27756 - 68
1717chain 'D' and (resid 278 through 290 )DD278 - 29069 - 81
1818chain 'D' and (resid 291 through 304 )DD291 - 30482 - 95
1919chain 'D' and (resid 305 through 328 )DD305 - 32896 - 112
2020chain 'D' and (resid 329 through 359 )DD329 - 359113 - 143
2121chain 'D' and (resid 360 through 378 )DD360 - 378144 - 162
2222chain 'D' and (resid 379 through 403 )DD379 - 403163 - 187
2323chain 'D' and (resid 404 through 446 )DD404 - 446188 - 222
2424chain 'D' and (resid 447 through 464 )DD447 - 464223 - 237
2525chain 'D' and (resid 465 through 477 )DD465 - 477238 - 250

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