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- PDB-6apv: Trypanosoma brucei hypoxanthine guanine phosphoribosyltransferase... -

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Basic information

Entry
Database: PDB / ID: 6apv
TitleTrypanosoma brucei hypoxanthine guanine phosphoribosyltransferase in complex with [(2-{[2-(2-amino-6-oxo-1,6-dihydro-9H-purin-9-yl)ethyl][(E)-2-phosphonoethenyl]amino}ethoxy)methyl]phosphonic acid
ComponentsHypoxanthine-guanine phosphoribosyltransferase
KeywordsTRANSFERASE / Trypanosoma brucei / Purine salvage / acyclic nucleoside biphosphonate
Function / homology
Function and homology information


hypoxanthine phosphoribosyltransferase / guanine phosphoribosyltransferase activity / hypoxanthine phosphoribosyltransferase activity / IMP salvage / glycosome / nuclear lumen / ciliary plasm / purine ribonucleoside salvage / nucleotide binding / metal ion binding ...hypoxanthine phosphoribosyltransferase / guanine phosphoribosyltransferase activity / hypoxanthine phosphoribosyltransferase activity / IMP salvage / glycosome / nuclear lumen / ciliary plasm / purine ribonucleoside salvage / nucleotide binding / metal ion binding / cytosol / cytoplasm
Similarity search - Function
Hypoxanthine phosphoribosyl transferase / Purine/pyrimidine phosphoribosyl transferases signature. / Rossmann fold - #2020 / Phosphoribosyl transferase domain / Phosphoribosyltransferase-like / Phosphoribosyltransferase domain / Rossmann fold / 3-Layer(aba) Sandwich / Alpha Beta
Similarity search - Domain/homology
Chem-3L4 / DI(HYDROXYETHYL)ETHER / Hypoxanthine-guanine phosphoribosyltransferase
Similarity search - Component
Biological speciesTrypanosoma brucei brucei (eukaryote)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.993 Å
AuthorsTeran, D. / Guddat, L.W.
CitationJournal: PLoS Negl Trop Dis / Year: 2018
Title: Evaluation of the Trypanosoma brucei 6-oxopurine salvage pathway as a potential target for drug discovery.
Authors: Dolezelova, E. / Teran, D. / Gahura, O. / Kotrbova, Z. / Prochazkova, M. / Keough, D. / Spacek, P. / Hockova, D. / Guddat, L. / Zikova, A.
History
DepositionAug 18, 2017Deposition site: RCSB / Processing site: RCSB
Revision 1.0Mar 14, 2018Provider: repository / Type: Initial release
Revision 1.1Oct 4, 2023Group: Data collection / Database references ...Data collection / Database references / Derived calculations / Refinement description
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / database_2 / pdbx_initial_refinement_model / pdbx_struct_conn_angle / struct_conn
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession ..._database_2.pdbx_DOI / _database_2.pdbx_database_accession / _pdbx_struct_conn_angle.ptnr1_auth_seq_id / _pdbx_struct_conn_angle.ptnr3_auth_seq_id / _pdbx_struct_conn_angle.value / _struct_conn.pdbx_dist_value / _struct_conn.pdbx_ptnr1_label_alt_id / _struct_conn.pdbx_ptnr2_label_alt_id / _struct_conn.ptnr1_auth_asym_id / _struct_conn.ptnr1_auth_comp_id / _struct_conn.ptnr1_auth_seq_id / _struct_conn.ptnr1_label_asym_id / _struct_conn.ptnr1_label_atom_id / _struct_conn.ptnr1_label_comp_id / _struct_conn.ptnr1_label_seq_id / _struct_conn.ptnr2_auth_asym_id / _struct_conn.ptnr2_auth_comp_id / _struct_conn.ptnr2_auth_seq_id / _struct_conn.ptnr2_label_asym_id / _struct_conn.ptnr2_label_atom_id / _struct_conn.ptnr2_label_comp_id

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Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

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Assembly

Deposited unit
A: Hypoxanthine-guanine phosphoribosyltransferase
B: Hypoxanthine-guanine phosphoribosyltransferase
C: Hypoxanthine-guanine phosphoribosyltransferase
D: Hypoxanthine-guanine phosphoribosyltransferase
hetero molecules


Theoretical massNumber of molelcules
Total (without water)99,25920
Polymers96,8874
Non-polymers2,37216
Water10,341574
1
A: Hypoxanthine-guanine phosphoribosyltransferase
B: Hypoxanthine-guanine phosphoribosyltransferase
hetero molecules


Theoretical massNumber of molelcules
Total (without water)49,63010
Polymers48,4442
Non-polymers1,1868
Water362
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area4400 Å2
ΔGint-31 kcal/mol
Surface area15100 Å2
MethodPISA
2
C: Hypoxanthine-guanine phosphoribosyltransferase
hetero molecules

D: Hypoxanthine-guanine phosphoribosyltransferase
hetero molecules


Theoretical massNumber of molelcules
Total (without water)49,63010
Polymers48,4442
Non-polymers1,1868
Water362
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
crystal symmetry operation3_483x-1/2,-y+3,-z-3/21
Buried area3510 Å2
ΔGint-45 kcal/mol
Surface area15120 Å2
MethodPISA
Unit cell
Length a, b, c (Å)89.480, 94.555, 109.692
Angle α, β, γ (deg.)90.00, 90.00, 90.00
Int Tables number18
Space group name H-MP21221

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Components

#1: Protein
Hypoxanthine-guanine phosphoribosyltransferase / / HGPRTase


Mass: 24221.775 Da / Num. of mol.: 4
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Trypanosoma brucei brucei (eukaryote) / Gene: HGPRT / Production host: Escherichia coli (E. coli)
References: UniProt: Q07010, hypoxanthine phosphoribosyltransferase
#2: Chemical
ChemComp-3L4 / [(2-{[2-(2-amino-6-oxo-1,6-dihydro-9H-purin-9-yl)ethyl][(E)-2-phosphonoethenyl]amino}ethoxy)methyl]phosphonic acid


Mass: 438.270 Da / Num. of mol.: 4 / Source method: obtained synthetically / Formula: C12H20N6O8P2
#3: Chemical
ChemComp-MG / MAGNESIUM ION


Mass: 24.305 Da / Num. of mol.: 8 / Source method: obtained synthetically / Formula: Mg
#4: Chemical
ChemComp-PEG / DI(HYDROXYETHYL)ETHER / Diethylene glycol


Mass: 106.120 Da / Num. of mol.: 4 / Source method: obtained synthetically / Formula: C4H10O3
#5: Water ChemComp-HOH / water / Water


Mass: 18.015 Da / Num. of mol.: 574 / 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: 2.39 Å3/Da / Density % sol: 48.64 %
Crystal growTemperature: 293.15 K / Method: vapor diffusion, hanging drop
Details: 25% PEG 3350, 0.2 M lithium sulfate and 0.1 M Bis-Tris

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Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: SYNCHROTRON / Site: Australian Synchrotron / Beamline: MX1 / Wavelength: 0.95369 Å
DetectorType: ADSC QUANTUM 270 / Detector: CCD / Date: Dec 6, 2016
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.95369 Å / Relative weight: 1
ReflectionResolution: 1.99→47.44 Å / Num. obs: 64145 / % possible obs: 99 % / Redundancy: 9.4 % / Rpim(I) all: 0.061 / Net I/σ(I): 12.3
Reflection shellResolution: 1.99→2.84 Å / Redundancy: 8.9 % / Mean I/σ(I) obs: 3.7 / Num. unique obs: 3961 / Rpim(I) all: 0.24 / % possible all: 84.3

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Processing

Software
NameVersionClassification
PHENIX(1.11.1_2575: ???)refinement
XDSdata reduction
XDSdata scaling
PHASERphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 5JSQ
Resolution: 1.993→47.278 Å / SU ML: 0.15 / Cross valid method: FREE R-VALUE / σ(F): 1.35 / Phase error: 18.59 / Stereochemistry target values: ML
RfactorNum. reflection% reflection
Rfree0.1981 2005 3.14 %
Rwork0.1636 --
obs0.1647 63913 99.55 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL
Refinement stepCycle: LAST / Resolution: 1.993→47.278 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms5599 0 148 574 6321
Refine LS restraints
Refine-IDTypeDev idealNumber
X-RAY DIFFRACTIONf_bond_d0.0096049
X-RAY DIFFRACTIONf_angle_d0.9988246
X-RAY DIFFRACTIONf_dihedral_angle_d12.0794957
X-RAY DIFFRACTIONf_chiral_restr0.064947
X-RAY DIFFRACTIONf_plane_restr0.0071040
LS refinement shell
Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkRefine-ID% reflection obs (%)
1.9929-2.04280.24141460.18544211X-RAY DIFFRACTION96
2.0428-2.0980.2091380.1734379X-RAY DIFFRACTION100
2.098-2.15970.19631400.15564369X-RAY DIFFRACTION100
2.1597-2.22940.17481410.16314410X-RAY DIFFRACTION100
2.2294-2.30910.2511330.19014371X-RAY DIFFRACTION100
2.3091-2.40160.21771540.15574412X-RAY DIFFRACTION100
2.4016-2.51080.20151470.15714389X-RAY DIFFRACTION100
2.5108-2.64320.21941440.15874413X-RAY DIFFRACTION100
2.6432-2.80880.18791420.16364428X-RAY DIFFRACTION100
2.8088-3.02560.21061390.16224447X-RAY DIFFRACTION100
3.0256-3.330.19051410.15954471X-RAY DIFFRACTION100
3.33-3.81170.2011450.16034475X-RAY DIFFRACTION100
3.8117-4.80160.15231490.14064497X-RAY DIFFRACTION100
4.8016-47.29080.20911460.18884636X-RAY DIFFRACTION98
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)
11.2622-0.5401-0.78982.39580.69753.2356-0.03270.0776-0.0014-0.05630.04860.0728-0.0481-0.0759-0.00060.08-0.0164-0.01810.08160.01310.095517.315499.7917-91.448
20.86380.62390.4727.52472.8662.4941-0.1798-0.7767-0.03890.56790.1399-1.19110.62551.2442-0.1090.28970.00780.05590.4771-0.06740.381433.81596.5224-100.5601
31.26320.3147-0.11392.1082-0.27981.7816-0.0241-0.05690.10690.17330.0516-0.2413-0.2020.2004-0.02770.094-0.0018-0.03450.1-0.01840.137824.3234109.2414-83.2516
44.55071.8952-2.73416.46321.28558.099-0.07980.43890.009-0.76020.12320.07380.2055-0.7383-0.06260.1861-0.0229-0.0640.1534-0.00770.196410.316479.2443-94.7306
51.52030.77280.4382.30450.5463.3344-0.0144-0.0833-0.05770.22480.01320.0976-0.015-0.1309-0.010.10790.0324-00.07780.02210.115617.374490.1473-72.2882
66.66720.7737-1.99334.60270.36275.21590.1388-0.06870.27280.09440.0244-0.6241-0.05670.6573-0.13030.09160.0303-0.03930.1420.01710.102226.123992.7051-75.3151
70.96380.31620.55843.65222.5855.60060.00910.05130.0259-0.23530.2771-0.5825-0.49840.3759-0.24330.1079-0.01430.00070.17680.00460.166728.072184.849-74.5281
81.62042.80782.15565.76763.96884.1139-0.0723-0.2531-0.02040.55270.276-1.06230.23020.9006-0.18060.2040.047-0.09430.2362-0.00930.391534.6581.1788-73.1809
91.2617-0.16950.11931.9424-0.07932.5061-0.0284-0.0343-0.16590.03920.0805-0.11830.19020.0846-0.05490.05390.0104-0.00420.0868-0.01620.144621.265879.2147-83.3692
103.3183-2.2734-1.32161.7873-0.05214.4378-0.14160.7027-0.6214-0.91810.0676-0.72930.69230.6480.1430.4859-0.03020.18240.4422-0.15630.395728.42877.9592-106.7512
114.1845-0.8049-2.67692.3849-0.62252.2843-0.2773-0.55860.13651.10040.1607-0.3377-0.02970.72850.13790.37740.0528-0.12530.2113-0.00860.247217.3221127.8992-73.1108
123.4941-1.21613.11423.0598-1.07088.3580.09020.2606-0.1077-0.15870.0138-0.29580.02140.5795-0.1240.076-0.00530.02190.0952-0.01580.171613.9686133.1264-93.8233
132.3906-0.55790.62652.59580.0532.3727-0.02840.0127-0.0317-0.21530.08870.1010.0214-0.0073-0.08040.0801-0.0084-0.02740.0601-0.00090.09833.567140.7635-94.7331
147.7306-0.4955-2.14975.13880.10625.81430.11170.01670.04360.0645-0.02940.4019-0.3604-0.4543-0.12320.085-0.0047-0.03740.0287-0.00340.08740.2342141.9254-92.0327
152.955-0.4931.11194.0312-1.76194.3316-0.3169-0.0598-0.06510.34730.35550.2848-0.562-0.32150.02850.08950.0241-0.02220.16110.03040.1908-3.0913132.8931-91.4561
162.4812-2.87623.77693.4356-3.91988.18410.1014-0.1340.1411-0.34710.08470.62080.479-0.7789-0.15390.1396-0.0427-0.05360.21620.03190.472-10.0687129.0217-91.3528
172.3249-0.71790.87151.0535-0.34013.1876-0.08180.0217-0.2298-0.36450.12490.35460.2769-0.2113-0.08220.1522-0.0694-0.10680.1370.02880.23530.0179127.8773-92.5255
185.74373.2588-1.61016.4791-2.16622.3615-0.23970.0754-0.0746-0.47180.20640.55050.4282-0.2847-0.00660.1485-0.0308-0.03780.1161-0.00780.2174-0.0567121.9348-91.4973
191.4906-0.4185-0.64522.5911-0.50911.2949-0.1067-0.2495-0.13290.50730.09310.0022-0.016-0.06090.02760.16310.0363-0.01970.13930.02750.10668.6617128.945-75.4236
205.3437-0.03454.0014.3953-3.34895.7392-0.2434-0.846-0.59710.61590.17210.45341.0102-0.54790.0850.7520.08690.20160.41070.09880.24013.6617124.41-61.8899
217.1558-0.0626-5.06527.6894-0.23115.126-0.0368-0.61770.30060.79460.1844-0.51120.03380.5281-0.12690.18030.0416-0.06670.1339-0.01970.250258.5657125.9591-69.5692
221.0159-0.2216-0.26580.08730.22738.4872-0.09290.1484-0.4048-0.49340.0495-0.73990.16970.4039-0.09380.3001-0.04410.20.1661-0.08880.254260.9371131.5539-90.4347
232.4316-0.76930.51781.53630.30210.8928-0.07970.2573-0.0092-0.70030.1137-0.01620.05010.057-0.02240.2989-0.06890.04130.1718-0.00860.130751.3014139.3011-93.2758
246.8271-2.8444-3.97384.08610.38676.19750.07540.2831-0.1872-0.59650.01890.4106-0.2781-0.4257-0.1150.2844-0.09210.00670.1713-0.00670.079547.5262140.8497-92.2073
251.9803-0.04340.84914.8873-3.25557.8852-0.27630.21550.1363-0.09340.3160.2161-0.7345-0.3863-0.09450.2404-0.0337-0.03730.2078-0.00540.129943.8633132.0089-92.6482
262.1883-2.19831.97646.0992-4.22927.1468-0.2150.45490.1075-0.98330.20020.95160.301-0.7555-0.08860.3093-0.1099-0.1170.2658-0.00490.311437.3093128.0892-94.0548
272.05570.4488-0.1960.84530.29121.8558-0.20390.4036-0.2976-0.75830.18030.00380.1177-0.106-0.04960.2841-0.0853-0.02260.1934-0.04520.176246.8227124.2375-92.3926
280.60161.6152-0.56025.777-1.98750.679-0.15420.0213-0.1284-0.23610.11750.19260.2187-0.10680.0810.0570.00430.02410.1181-0.02050.205552.3082120.9611-78.8592
293.8031-0.57660.09343.41650.16112.4896-0.0672-0.0937-0.25640.20320.1010.08570.1701-0.0524-0.0410.09880.00720.02560.06950.00070.094150.4112130.4174-72.0207
305.57163.0798-2.11.7562-0.76743.6395-0.2844-0.8-0.92090.70250.39410.9290.5842-0.52060.15440.40660.01140.15740.37780.16980.414741.1311124.4682-60.5593
Refinement TLS group
IDRefine-IDRefine TLS-IDSelection details
1X-RAY DIFFRACTION1chain 'A' and (resid 5 through 80 )
2X-RAY DIFFRACTION2chain 'A' and (resid 81 through 107 )
3X-RAY DIFFRACTION3chain 'A' and (resid 108 through 200 )
4X-RAY DIFFRACTION4chain 'B' and (resid 5 through 16 )
5X-RAY DIFFRACTION5chain 'B' and (resid 17 through 69 )
6X-RAY DIFFRACTION6chain 'B' and (resid 70 through 83 )
7X-RAY DIFFRACTION7chain 'B' and (resid 84 through 119 )
8X-RAY DIFFRACTION8chain 'B' and (resid 120 through 132 )
9X-RAY DIFFRACTION9chain 'B' and (resid 133 through 188 )
10X-RAY DIFFRACTION10chain 'B' and (resid 189 through 205 )
11X-RAY DIFFRACTION11chain 'C' and (resid 5 through 16 )
12X-RAY DIFFRACTION12chain 'C' and (resid 17 through 34 )
13X-RAY DIFFRACTION13chain 'C' and (resid 35 through 69 )
14X-RAY DIFFRACTION14chain 'C' and (resid 70 through 80 )
15X-RAY DIFFRACTION15chain 'C' and (resid 81 through 119 )
16X-RAY DIFFRACTION16chain 'C' and (resid 120 through 132 )
17X-RAY DIFFRACTION17chain 'C' and (resid 133 through 148 )
18X-RAY DIFFRACTION18chain 'C' and (resid 149 through 158 )
19X-RAY DIFFRACTION19chain 'C' and (resid 159 through 188 )
20X-RAY DIFFRACTION20chain 'C' and (resid 189 through 199 )
21X-RAY DIFFRACTION21chain 'D' and (resid 5 through 16 )
22X-RAY DIFFRACTION22chain 'D' and (resid 17 through 34 )
23X-RAY DIFFRACTION23chain 'D' and (resid 35 through 69 )
24X-RAY DIFFRACTION24chain 'D' and (resid 70 through 80 )
25X-RAY DIFFRACTION25chain 'D' and (resid 81 through 119 )
26X-RAY DIFFRACTION26chain 'D' and (resid 120 through 132 )
27X-RAY DIFFRACTION27chain 'D' and (resid 133 through 158 )
28X-RAY DIFFRACTION28chain 'D' and (resid 159 through 168 )
29X-RAY DIFFRACTION29chain 'D' and (resid 169 through 188 )
30X-RAY DIFFRACTION30chain 'D' and (resid 189 through 201 )

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