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- PDB-4dx1: Crystal structure of the human TRPV4 ankyrin repeat domain -

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Basic information

Entry
Database: PDB / ID: 4dx1
TitleCrystal structure of the human TRPV4 ankyrin repeat domain
ComponentsTransient receptor potential cation channel subfamily V member 4
KeywordsTRANSPORT PROTEIN / Ankyrin Repeat / Ion Channel / Menbrane
Function / homology
Function and homology information


blood vessel endothelial cell delamination / osmosensor activity / vasopressin secretion / stretch-activated, monoatomic cation-selective, calcium channel activity / positive regulation of striated muscle contraction / calcium ion import into cytosol / positive regulation of macrophage inflammatory protein 1 alpha production / negative regulation of brown fat cell differentiation / positive regulation of microtubule depolymerization / hyperosmotic salinity response ...blood vessel endothelial cell delamination / osmosensor activity / vasopressin secretion / stretch-activated, monoatomic cation-selective, calcium channel activity / positive regulation of striated muscle contraction / calcium ion import into cytosol / positive regulation of macrophage inflammatory protein 1 alpha production / negative regulation of brown fat cell differentiation / positive regulation of microtubule depolymerization / hyperosmotic salinity response / cortical microtubule organization / regulation of response to osmotic stress / positive regulation of chemokine (C-X-C motif) ligand 1 production / positive regulation of chemokine (C-C motif) ligand 5 production / cartilage development involved in endochondral bone morphogenesis / cellular hypotonic response / cellular hypotonic salinity response / multicellular organismal-level water homeostasis / positive regulation of vascular permeability / cellular response to osmotic stress / calcium ion import / osmosensory signaling pathway / cell volume homeostasis / positive regulation of monocyte chemotactic protein-1 production / cell-cell junction assembly / TRP channels / regulation of aerobic respiration / cortical actin cytoskeleton / positive regulation of macrophage chemotaxis / beta-tubulin binding / diet induced thermogenesis / microtubule polymerization / cytoplasmic microtubule / calcium ion import across plasma membrane / alpha-tubulin binding / monoatomic cation channel activity / response to mechanical stimulus / SH2 domain binding / filopodium / calcium ion transmembrane transport / actin filament organization / protein kinase C binding / adherens junction / positive regulation of JNK cascade / calcium channel activity / response to insulin / cilium / ruffle membrane / intracellular calcium ion homeostasis / positive regulation of inflammatory response / calcium ion transport / positive regulation of interleukin-6 production / actin filament binding / negative regulation of neuron projection development / lamellipodium / glucose homeostasis / actin binding / cellular response to heat / positive regulation of cytosolic calcium ion concentration / growth cone / actin cytoskeleton organization / microtubule binding / positive regulation of ERK1 and ERK2 cascade / calmodulin binding / response to hypoxia / apical plasma membrane / focal adhesion / lipid binding / protein kinase binding / negative regulation of transcription by RNA polymerase II / cell surface / endoplasmic reticulum / ATP binding / identical protein binding / membrane / metal ion binding / plasma membrane
Similarity search - Function
Transient receptor potential cation channel subfamily V member 4 / Ankyrin repeat-containing domain / Transient receptor potential cation channel subfamily V member 1-4 / Transient receptor potential cation channel subfamily V / Ankyrin repeat / Ankyrin repeat profile. / Ankyrin repeat region circular profile. / ankyrin repeats / Ankyrin repeat / Ankyrin repeat-containing domain superfamily ...Transient receptor potential cation channel subfamily V member 4 / Ankyrin repeat-containing domain / Transient receptor potential cation channel subfamily V member 1-4 / Transient receptor potential cation channel subfamily V / Ankyrin repeat / Ankyrin repeat profile. / Ankyrin repeat region circular profile. / ankyrin repeats / Ankyrin repeat / Ankyrin repeat-containing domain superfamily / Serine Threonine Protein Phosphatase 5, Tetratricopeptide repeat / Ion transport domain / Ion transport protein / Alpha Horseshoe / Mainly Alpha
Similarity search - Domain/homology
PHOSPHATE ION / Transient receptor potential cation channel subfamily V member 4
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / molecular replacement / Resolution: 2.85 Å
AuthorsInada, H. / Gaudet, R.
CitationJournal: Biochemistry / Year: 2012
Title: Structural and biochemical consequences of disease-causing mutations in the ankyrin repeat domain of the human TRPV4 channel.
Authors: Inada, H. / Procko, E. / Sotomayor, M. / Gaudet, R.
History
DepositionFeb 27, 2012Deposition site: RCSB / Processing site: RCSB
Revision 1.0Jul 18, 2012Provider: repository / Type: Initial release
Revision 1.1Dec 19, 2012Group: Database references
Revision 1.2Feb 28, 2024Group: Data collection / Database references / Derived calculations
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / database_2 / struct_ref_seq_dif / struct_site
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession ..._database_2.pdbx_DOI / _database_2.pdbx_database_accession / _struct_ref_seq_dif.details / _struct_site.pdbx_auth_asym_id / _struct_site.pdbx_auth_comp_id / _struct_site.pdbx_auth_seq_id

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Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

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Assembly

Deposited unit
A: Transient receptor potential cation channel subfamily V member 4
B: Transient receptor potential cation channel subfamily V member 4
hetero molecules


Theoretical massNumber of molelcules
Total (without water)59,4808
Polymers58,9132
Non-polymers5676
Water30617
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A: Transient receptor potential cation channel subfamily V member 4
hetero molecules


Theoretical massNumber of molelcules
Total (without water)29,7394
Polymers29,4571
Non-polymers2823
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
2
B: Transient receptor potential cation channel subfamily V member 4
hetero molecules


Theoretical massNumber of molelcules
Total (without water)29,7424
Polymers29,4571
Non-polymers2853
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Unit cell
Length a, b, c (Å)53.370, 53.370, 440.711
Angle α, β, γ (deg.)90.000, 90.000, 120.000
Int Tables number152
Space group name H-MP3121

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Components

#1: Protein Transient receptor potential cation channel subfamily V member 4 / TrpV4 / Osm-9-like TRP channel 4 / OTRPC4 / Transient receptor potential protein 12 / TRP12 / ...TrpV4 / Osm-9-like TRP channel 4 / OTRPC4 / Transient receptor potential protein 12 / TRP12 / Vanilloid receptor-like channel 2 / Vanilloid receptor-like protein 2 / VRL-2 / Vanilloid receptor-related osmotically-activated channel / VR-OAC


Mass: 29456.746 Da / Num. of mol.: 2 / Fragment: N-terminal domain (UNP residues 149-397)
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: TRPV4, VRL2, VROAC / Production host: Escherichia coli (E. coli) / Strain (production host): BL21(DE3) / References: UniProt: Q9HBA0
#2: Chemical
ChemComp-PO4 / PHOSPHATE ION


Mass: 94.971 Da / Num. of mol.: 5 / Source method: obtained synthetically / Formula: PO4
#3: Chemical ChemComp-GOL / GLYCEROL / GLYCERIN / PROPANE-1,2,3-TRIOL


Mass: 92.094 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C3H8O3
#4: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 17 / Source method: isolated from a natural source / Formula: H2O

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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: 3.08 Å3/Da / Density % sol: 60.01 %
Crystal growTemperature: 277 K / Method: vapor diffusion, hanging drop / pH: 7.8
Details: 0.35M sodium potassium phosphate, 0.1M HEPES, 10% glycerol, pH 7.8, VAPOR DIFFUSION, HANGING DROP, temperature 277K

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Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: SYNCHROTRON / Site: APS / Beamline: 24-ID-E / Wavelength: 0.9792 Å
DetectorType: ADSC QUANTUM 315 / Detector: CCD / Date: Mar 17, 2010
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.9792 Å / Relative weight: 1
ReflectionResolution: 2.85→40 Å / Num. obs: 18334 / % possible obs: 99.6 % / Redundancy: 5.3 % / Rmerge(I) obs: 0.115 / Χ2: 1.053 / Net I/σ(I): 12.3
Reflection shell
Resolution (Å)Redundancy (%)Rmerge(I) obsNum. unique allΧ2Diffraction-ID% possible all
2.85-2.95.40.6418981.019199.3
2.9-2.955.50.5679071.035199.6
2.95-3.015.60.4848651.059199.3
3.01-3.075.40.4098691.0971100
3.07-3.145.30.3359431.09199.7
3.14-3.215.70.2788511.089199
3.21-3.295.40.2449021.0771100
3.29-3.385.50.228771.075199.8
3.38-3.485.50.1768661.072199.4
3.48-3.595.30.1669461.0311100
3.59-3.725.50.1538821.054199.5
3.72-3.875.30.1379221.052199.9
3.87-4.045.50.1428901.044199.8
4.04-4.265.30.1319251.043199.9
4.26-4.525.30.1349151.055199.6
4.52-4.875.20.1319551.041100
4.87-5.365.20.1319371.0231100
5.36-6.135.20.119310.995199.1
6.13-7.7250.0769921.099199.4
7.72-404.80.04910611.008198.9

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Phasing

PhasingMethod: molecular replacement
Phasing MR
Highest resolutionLowest resolution
Rotation3.15 Å39.12 Å
Translation3.15 Å39.12 Å

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Processing

Software
NameVersionClassificationNB
SCALEPACKdata scaling
MOLREPphasing
REFMACrefinement
PDB_EXTRACT3.1data extraction
HKL-2000data reduction
RefinementMethod to determine structure: MOLECULAR REPLACEMENT / Resolution: 2.85→39.12 Å / Cor.coef. Fo:Fc: 0.943 / Cor.coef. Fo:Fc free: 0.931 / WRfactor Rfree: 0.3066 / WRfactor Rwork: 0.2296 / Occupancy max: 1 / Occupancy min: 1 / FOM work R set: 0.7421 / SU B: 48.665 / SU ML: 0.394 / SU R Cruickshank DPI: 1.1525 / SU Rfree: 0.3903 / Cross valid method: THROUGHOUT / σ(F): 0 / ESU R: 1.153 / ESU R Free: 0.39 / Stereochemistry target values: MAXIMUM LIKELIHOOD
Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS. U VALUES: WITH TLS ADDED
RfactorNum. reflection% reflectionSelection details
Rfree0.2785 930 5.1 %RANDOM
Rwork0.2152 ---
obs0.2184 18236 99.58 %-
Solvent computationIon probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.4 Å / Solvent model: MASK
Displacement parametersBiso max: 184.43 Å2 / Biso mean: 81.1238 Å2 / Biso min: 49.8 Å2
Baniso -1Baniso -2Baniso -3
1-0.46 Å20.23 Å20 Å2
2--0.46 Å20 Å2
3----0.69 Å2
Refinement stepCycle: LAST / Resolution: 2.85→39.12 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms3981 0 31 17 4029
Refine LS restraints
Refine-IDTypeDev idealDev ideal targetNumber
X-RAY DIFFRACTIONr_bond_refined_d0.0130.0224084
X-RAY DIFFRACTIONr_angle_refined_deg1.5131.9765519
X-RAY DIFFRACTIONr_dihedral_angle_1_deg6.3345497
X-RAY DIFFRACTIONr_dihedral_angle_2_deg35.78523.166199
X-RAY DIFFRACTIONr_dihedral_angle_3_deg19.76615720
X-RAY DIFFRACTIONr_dihedral_angle_4_deg18.2961540
X-RAY DIFFRACTIONr_chiral_restr0.0920.2613
X-RAY DIFFRACTIONr_gen_planes_refined0.0070.0213086
X-RAY DIFFRACTIONr_mcbond_it0.4511.52487
X-RAY DIFFRACTIONr_mcangle_it0.85524012
X-RAY DIFFRACTIONr_scbond_it1.21331597
X-RAY DIFFRACTIONr_scangle_it2.0864.51507
LS refinement shellResolution: 2.851→2.924 Å / Total num. of bins used: 20
RfactorNum. reflection% reflection
Rfree0.358 75 -
Rwork0.326 1241 -
all-1316 -
obs--99.4 %
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)
123.1977-1.3394-4.7468.27024.05755.77320.1168-0.65960.82630.6839-0.1585-0.3931-1.2815-0.19880.04170.7946-0.1245-0.00930.2761-0.08680.357421.062-0.66211.651
22.3013-2.8807-5.698812.1672-1.92757.26470.0102-0.1516-0.07011.01670.08180.8828-0.4022-0.2999-0.09210.4051-0.10330.08260.2964-0.02590.5410.915-9.33912.453
3-2.75464.1079-9.265332.5148-42.832743.42570.81770.74620.679-0.67730.54860.6832-0.2022-1.5742-1.36630.82730.21570.19730.81960.0310.443812.379-1.3832.545
418.3967-10.644612.83837.6801-7.195510.8283-1.20410.51790.69831.3345-0.1015-0.5943-1.8902-0.59871.30561.0102-0.0115-0.15150.4797-0.18070.592720.5580.944-0.084
55.05660.11561.55781.9436-1.77747.93610.2806-0.5565-0.18720.3685-0.2548-0.39540.05790.9748-0.02580.2707-0.15470.0170.486-0.05680.553229.612-7.5984.682
6-4.54843.216-6.1945-4.14250.999458.3696-0.19750.0439-0.1039-0.12140.29090.10731.58630.217-0.09340.4527-0.09070.07150.45920.09250.613415.556-15.4826.096
720.327313.81373.34714.3936-10.799125.2580.27641.5785-0.5088-0.5830.7510.39531.5444-0.3825-1.02740.478-0.26880.04210.6278-0.22840.657215.981-11.183-3.671
826.264818.2865-4.677113.79411.026813.17860.12-0.77860.98590.0743-0.8921.2071-0.4596-0.23040.77190.403-0.00280.02260.3703-0.14580.57520.4815.334-10.379
9-4.44690.174-1.55653.30016.906711.3719-0.05040.07720.17270.1478-0.1854-0.08430.4883-0.53510.23590.5057-0.14220.07020.30210.02070.566126.366-3.3-8.906
1039.81345.0122-18.515543.3103-18.57248.30992.59271.47870.49181.148-1.63530.82330.15625.3891-0.95741.23620.1630.16881.8702-0.0440.442636.037-6.623-4.837
1113.8662-4.3926-3.101713.63923.815918.22690.0976-0.6318-1.48120.8030.2703-0.0630.53820.0268-0.36790.5049-0.01760.08640.30440.07160.457528.283-13.763-3.994
125.2621-2.37133.0025-0.33521.95186.5511-0.3380.34290.5528-0.5447-0.10990.1734-1.0048-0.53030.44790.6329-0.2128-0.00440.54640.15810.769822.5166.136-15.356
13-0.1625-3.0334-7.8847-2.82462.427713.4610.44440.35770.0123-0.085-0.0956-0.0077-0.6395-0.8548-0.34880.5298-0.1589-0.02670.37440.04850.700727.814-0.353-18.432
146.54062.3579-3.08982.8136-1.336212.6276-0.3945-0.2895-0.16850.24590.0807-0.47580.78480.91550.31380.44920.00630.08480.2589-0.05670.457435.083-10.819-15.299
153.05340.3041-1.813217.5967-4.7167.262-0.14860.6225-0.3055-0.47540.06370.10890.9771-0.72430.08490.4407-0.1319-0.00610.255-0.1270.365925.567-11.105-21.853
164.79442.74670.52579.58282.79756.17840.3840.2293-0.02540.3379-0.2979-0.80510.57350.576-0.0860.353-0.00350.09950.30460.01940.385640.81-5.703-25.035
1773.245568.7439-10.451631.35575.592144.64371.42291.4699-1.26071.12882.7424-0.22871.505-0.8683-4.16531.4605-0.2470.02110.1084-0.27571.072131.604-22.413-27.824
1817.161-10.90161.389919.4742-13.46895.5898-0.18610.4462-0.7538-1.78360.30030.32361.048-0.6298-0.11420.728-0.044-0.07020.3669-0.10640.284926.876-8.373-34.035
196.8593-4.3178-3.931318.15370.64724.4278-0.1082-0.08680.39110.24790.4699-0.46220.33620.0518-0.36180.45250.04350.08050.2499-0.02990.269937.546-0.553-34.854
204.0855-20.1542-13.245940.223817.48836.7309-0.1401-0.3556-0.01960.17810.8141-0.59520.64460.0646-0.6741.1980.1182-0.14160.47280.00990.571642.709-12.726-37.864
213.5679-3.38455.82248.49351.035512.0109-0.35980.59150.37810.30480.59881.384-0.5695-0.6175-0.23890.4905-0.0284-0.01830.80460.3680.9169-8.19532.362-81.555
224.33490.1429-3.964411.7516-2.383810.6070.05280.52850.6156-0.307-0.056-0.1726-0.88990.65290.00330.4226-0.0051-0.01920.3321-0.03190.4744.41136.733-80.305
237.8447.1164-16.70413.7621-4.658620.54090.2969-0.54740.77680.94810.20750.8609-0.23450.0018-0.50430.68490.14410.07880.30540.06750.6792-3.16734.776-70.183
242.65740.2449-2.8295-2.2778-2.08492.3460.15420.36880.4434-0.01930.1110.4907-0.978-0.6068-0.26520.8560.1743-0.29180.40730.02481.0793-9.31628.401-70.196
2510.78371.8777-3.186.0443-1.77681.0361-0.80150.6093-0.7524-0.47980.74750.63280.5196-0.05630.0540.5608-0.0638-0.09090.3918-0.00440.6334-6.38819.559-79.939
2616.48930.118812.5881-3.7807-4.29849.39730.37980.7316-0.7142-0.39550.19920.13320.17630.4453-0.57890.703-0.05270.0240.3538-0.10640.58837.42827.565-77.664
279.699711.8832-0.22747.8562.935830.2008-0.0886-0.5159-0.65190.74930.0593-0.90941.19871.28880.02930.56920.1857-0.0820.5093-0.02440.85663.53424.984-68.161
2812.06774.4207-1.38626.95781.24692.15760.31630.50960.9490.8821-0.27740.1017-0.2998-0.3816-0.03890.62170.14920.01690.3110.04860.6651-12.90925.855-60.205
291.3307-2.00442.103311.9663-1.36521.8473-0.79250.66490.282-0.31010.57820.53711.39770.35080.21430.6916-0.06780.13740.43150.09930.5683-9.24114.522-69.38
30-5.62350.23392.58618.6339-10.057311.9262-0.82290.3583-0.3074-1.02060.3196-0.9574-0.34460.79270.50320.8727-0.0590.35750.4042-0.01080.783-0.00914.459-72.812
3122.2553-0.0276-1.51621.1002-1.62085.8224-0.7376-0.69752.30640.71770.4575-0.3685-0.2362-0.02960.28010.66760.1381-0.05410.308-0.17160.6366-13.1722.898-56.545
32-0.27717.2029-2.8255.5543-4.81740.62160.4461-0.29080.41380.2915-0.19040.08010.2329-0.205-0.25570.74380.03310.15830.7586-0.05530.5124-18.96617.09-57.519
339.9179-13.27060.62727.1475-5.3134-2.71360.49350.16520.92370.1072-0.9572-0.7826-0.1150.52190.46360.989-0.20050.11330.67110.01930.5816-7.68911.508-59.324
3421.70092.6212-4.52498.49310.55613.55680.1851.2796-0.5834-0.5426-0.1363-0.50440.1933-0.1269-0.04870.76640.20050.09760.2691-0.00220.4219-3.8774.806-66.141
350.2337-1.7818-0.15893.31610.23117.5220.3534-0.14070.04810.1249-0.4894-0.10720.7803-0.05010.13590.7175-0.09060.07590.45960.03090.3719-9.9045.476-55.686
369.6646-4.36053.13214.6847-5.931810.1129-0.09430.1166-0.0409-0.9395-0.5885-0.71010.35180.70660.68280.8310.26660.16430.18510.07210.6077-2.04-2.294-56.597
372.93890.79232.43940.434-3.72676.9020.1876-0.0387-0.4140.07-0.5582-0.78160.22281.29460.37060.64860.06610.040.41190.12010.54-3.0043.233-45.342
383.3394-0.8375-1.17712.0398-4.60821.3523-0.2242-0.2936-0.19270.2031-0.0883-0.19020.01720.03680.31260.51550.0050.06520.2439-0.01660.4436-14.3134.304-43.049
3915.352-10.1682-9.32678.59553.14433.76080.0092-0.3413-1.3536-1.1698-0.37821.45540.76370.4310.3690.7020.12760.00670.4658-0.05340.4321-17.662-4.134-48.918
4016.1687-2.47470.283311.5219-20.2083.15080.35212.209-0.1203-0.33270.3790.26860.19430.1842-0.73111.15250.2422-0.04240.4366-0.05690.6286-9.605-11.316-49.02
Refinement TLS group
IDRefine-IDRefine TLS-IDAuth asym-IDAuth seq-ID
1X-RAY DIFFRACTION1A148 - 166
2X-RAY DIFFRACTION2A167 - 179
3X-RAY DIFFRACTION3A180 - 187
4X-RAY DIFFRACTION4A188 - 199
5X-RAY DIFFRACTION5A200 - 215
6X-RAY DIFFRACTION6A216 - 221
7X-RAY DIFFRACTION7A222 - 229
8X-RAY DIFFRACTION8A230 - 237
9X-RAY DIFFRACTION9A238 - 247
10X-RAY DIFFRACTION10A248 - 252
11X-RAY DIFFRACTION11A253 - 260
12X-RAY DIFFRACTION12A261 - 280
13X-RAY DIFFRACTION13A281 - 289
14X-RAY DIFFRACTION14A290 - 306
15X-RAY DIFFRACTION15A307 - 327
16X-RAY DIFFRACTION16A328 - 353
17X-RAY DIFFRACTION17A354 - 358
18X-RAY DIFFRACTION18A359 - 373
19X-RAY DIFFRACTION19A374 - 389
20X-RAY DIFFRACTION20A390 - 397
21X-RAY DIFFRACTION21B148 - 166
22X-RAY DIFFRACTION22B167 - 179
23X-RAY DIFFRACTION23B180 - 187
24X-RAY DIFFRACTION24B188 - 199
25X-RAY DIFFRACTION25B200 - 215
26X-RAY DIFFRACTION26B216 - 221
27X-RAY DIFFRACTION27B222 - 229
28X-RAY DIFFRACTION28B230 - 238
29X-RAY DIFFRACTION29B239 - 252
30X-RAY DIFFRACTION30B253 - 260
31X-RAY DIFFRACTION31B261 - 276
32X-RAY DIFFRACTION32B277 - 285
33X-RAY DIFFRACTION33B286 - 293
34X-RAY DIFFRACTION34B294 - 308
35X-RAY DIFFRACTION35B309 - 343
36X-RAY DIFFRACTION36B344 - 358
37X-RAY DIFFRACTION37B359 - 368
38X-RAY DIFFRACTION38B369 - 380
39X-RAY DIFFRACTION39B381 - 390
40X-RAY DIFFRACTION40B391 - 396

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