[English] 日本語
Yorodumi
- PDB-8ts4: Crystal structure of T. Brucei hypoxanthine guanine phosphoribosy... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 8ts4
TitleCrystal structure of T. Brucei hypoxanthine guanine phosphoribosyltransferase in complex with [2S,4S]-4-Guanin-9-yl-2-(2-phosphonoethoxymethyl)-1-N-(3-phosphonopropionyl)pyrrolidine
ComponentsHypoxanthine-guanine phosphoribosyltransferase
KeywordsTRANSFERASE / Inhibitor / complex / purine base / product analog
Function / homology
Function and homology information


hypoxanthine phosphoribosyltransferase / guanine phosphoribosyltransferase activity / guanine salvage / hypoxanthine metabolic process / hypoxanthine phosphoribosyltransferase activity / GMP salvage / IMP salvage / glycosome / ciliary plasm / nuclear lumen ...hypoxanthine phosphoribosyltransferase / guanine phosphoribosyltransferase activity / guanine salvage / hypoxanthine metabolic process / hypoxanthine phosphoribosyltransferase activity / GMP salvage / IMP salvage / glycosome / ciliary plasm / nuclear lumen / purine ribonucleoside salvage / nucleotide binding / magnesium ion binding / cytoplasm / cytosol
Similarity search - Function
Hypoxanthine phosphoribosyl transferase / : / Purine/pyrimidine phosphoribosyl transferases signature. / Phosphoribosyl transferase domain / Phosphoribosyltransferase-like / Phosphoribosyltransferase domain
Similarity search - Domain/homology
: / Hypoxanthine-guanine phosphoribosyltransferase
Similarity search - Component
Biological speciesTrypanosoma brucei (eukaryote)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.2 Å
AuthorsGuddat, L.W. / Guddat, L.W.
Funding support Australia, 1items
OrganizationGrant numberCountry
National Health and Medical Research Council (NHMRC, Australia)1147368 Australia
CitationJournal: J.Med.Chem. / Year: 2024
Title: Development of Prolinol Containing Inhibitors of Hypoxanthine-Guanine-Xanthine Phosphoribosyltransferase: Rational Structure-Based Drug Design.
Authors: Keough, D.T. / Petrova, M. / King, G. / Kratochvil, M. / Pohl, R. / Dolezelova, E. / Zikova, A. / Guddat, L.W. / Rejman, D.
History
DepositionAug 10, 2023Deposition site: RCSB / Processing site: RCSB
Revision 1.0May 8, 2024Provider: repository / Type: Initial release
Revision 1.1May 22, 2024Group: Database references / Category: citation / citation_author
Item: _citation.journal_volume / _citation.page_first ..._citation.journal_volume / _citation.page_first / _citation.page_last / _citation_author.identifier_ORCID

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

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


Theoretical massNumber of molelcules
Total (without water)47,8236
Polymers46,7862
Non-polymers1,0374
Water4,828268
1


  • Idetical with deposited unit
  • defined by author&software
  • Evidence: assay for oligomerization, DIMER
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area3170 Å2
ΔGint-30 kcal/mol
Surface area15320 Å2
MethodPISA
Unit cell
Length a, b, c (Å)93.031, 93.031, 105.701
Angle α, β, γ (deg.)90.000, 90.000, 90.000
Int Tables number94
Space group name H-MP42212
Space group name HallP4n2n
Symmetry operation#1: x,y,z
#2: -y+1/2,x+1/2,z+1/2
#3: y+1/2,-x+1/2,z+1/2
#4: x+1/2,-y+1/2,-z+1/2
#5: -x+1/2,y+1/2,-z+1/2
#6: -x,-y,z
#7: y,x,-z
#8: -y,-x,-z
Components on special symmetry positions
IDModelComponents
11A-529-

HOH

21B-466-

HOH

-
Components

#1: Protein Hypoxanthine-guanine phosphoribosyltransferase / HGPRT / HGPRTase


Mass: 23392.893 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Trypanosoma brucei (eukaryote) / Gene: HGPRT / Production host: Escherichia coli (E. coli)
References: UniProt: Q07010, hypoxanthine phosphoribosyltransferase
#2: Chemical ChemComp-MG / MAGNESIUM ION


Mass: 24.305 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: Mg
#3: Chemical ChemComp-KFF / (3-{(2S,4S)-4-(2-amino-6-oxo-1,6-dihydro-9H-purin-9-yl)-2-[(2-phosphonoethoxy)methyl]pyrrolidin-1-yl}-3-oxopropyl)phosphonic acid


Mass: 494.333 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C15H24N6O9P2 / Feature type: SUBJECT OF INVESTIGATION
#4: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 268 / Source method: isolated from a natural source / Formula: H2O
Has ligand of interestY

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 2.44 Å3/Da / Density % sol: 49.68 %
Crystal growTemperature: 293 K / Method: vapor diffusion, hanging drop / Details: 0.2 M MgCl2 , 0.1 M Bis-Tris, pH 5.0, 20% 3350 / PH range: 5

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: Australian Synchrotron / Beamline: MX1 / Wavelength: 0.95373 Å
DetectorType: DECTRIS PILATUS 2M / Detector: PIXEL / Date: Jul 5, 2020
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.95373 Å / Relative weight: 1
ReflectionResolution: 2.19651→45.9529 Å / Num. obs: 24294 / % possible obs: 99.92 % / Redundancy: 4 % / Biso Wilson estimate: 27.83 Å2 / CC1/2: 0.99 / Net I/σ(I): 18.4
Reflection shellResolution: 2.2→2.25 Å / Mean I/σ(I) obs: 3.5 / Num. unique obs: 1680 / CC1/2: 0.99

-
Processing

Software
NameVersionClassification
PHENIX1.21_5207refinement
XDSdata reduction
XDSdata scaling
PHENIXphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT / Resolution: 2.2→45.95 Å / SU ML: 0.2056 / Cross valid method: FREE R-VALUE / σ(F): 1.36 / Phase error: 20.8364
Stereochemistry target values: GeoStd + Monomer Library + CDL v1.2
RfactorNum. reflection% reflection
Rfree0.2217 2000 8.23 %
Rwork0.1708 22294 -
obs0.175 24294 99.94 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.1 Å / Solvent model: FLAT BULK SOLVENT MODEL
Displacement parametersBiso mean: 34.48 Å2
Refinement stepCycle: LAST / Resolution: 2.2→45.95 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms2774 0 66 268 3108
Refine LS restraints
Refine-IDTypeDev idealNumber
X-RAY DIFFRACTIONf_bond_d0.00862905
X-RAY DIFFRACTIONf_angle_d1.02513954
X-RAY DIFFRACTIONf_chiral_restr0.0572461
X-RAY DIFFRACTIONf_plane_restr0.0116491
X-RAY DIFFRACTIONf_dihedral_angle_d17.03191081
LS refinement shell
Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkRefine-ID% reflection obs (%)
2.2-2.250.25151380.18131542X-RAY DIFFRACTION99.29
2.25-2.310.2621420.17331581X-RAY DIFFRACTION100
2.31-2.380.23981390.17571557X-RAY DIFFRACTION100
2.38-2.460.24931400.17841556X-RAY DIFFRACTION100
2.46-2.540.23791410.16841565X-RAY DIFFRACTION100
2.55-2.650.19991410.17211578X-RAY DIFFRACTION100
2.65-2.770.2481410.17641565X-RAY DIFFRACTION100
2.77-2.910.24631410.16511576X-RAY DIFFRACTION100
2.91-3.10.23461420.18531585X-RAY DIFFRACTION100
3.1-3.330.24671430.1861590X-RAY DIFFRACTION99.94
3.33-3.670.21551430.16831599X-RAY DIFFRACTION100
3.67-4.20.21021450.1551614X-RAY DIFFRACTION100
4.2-5.290.16751480.14711637X-RAY DIFFRACTION99.94
5.29-45.950.23051560.18911749X-RAY DIFFRACTION100
Refinement TLS params.

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

IDL11 (°2)L12 (°2)L13 (°2)L22 (°2)L23 (°2)L33 (°2)S11 (Å °)S12 (Å °)S13 (Å °)S21 (Å °)S22 (Å °)S23 (Å °)S31 (Å °)S32 (Å °)S33 (Å °)T11 (Å2)T12 (Å2)T13 (Å2)T22 (Å2)T23 (Å2)T33 (Å2)Origin x (Å)Origin y (Å)Origin z (Å)
17.726369064560.595351740113-0.3048281845755.362025427094.799037840084.375208959210.1182214531791.001789544191.06250830412-0.872870083764-0.02901809939910.459261696102-1.51909468474-0.6456866721140.03531014746640.3403569104150.124689914280.03888581348760.5292118514390.2168246452570.5930264067929.28651471334.8794092101419.0407355994
22.540233698380.0752966898681-0.4921944861452.63457513951-0.4440370287854.293830934820.221490705672-0.2361775321690.2910459603520.334131867308-0.09466277330740.215620246339-0.0920580316066-0.120943285956-0.1296773164240.14896626123-0.05873127811370.04670778639410.188179837348-0.02040013047350.20422829177220.4758730358-7.3601461825140.4941390903
33.096789157543.097879443410.2617807144445.012905041-2.502426521427.93867465140.289479221335-0.0381375957174-0.4098402557350.116547687769-0.12086106126-0.1234804862160.5143785537650.405069274224-0.2246871496890.1789962616950.02743564647530.01540022648350.169456826928-0.03132572310750.22575508994115.8593498644-17.490791811338.8833970381
43.7907678349-2.907689993925.307748260365.71655494994-3.302048158817.826143764430.580580761502-0.00613305501552-0.8500338648550.0513943034042-0.05551021996810.5247829506960.89345870196-0.526412208148-0.3886941981670.218139653645-0.07863228164920.01172146702820.269710643141-0.03600910119970.30285444941711.2498293047-24.050430757637.9626028985
55.577103061710.4656984943340.8996021002782.003526453780.07823061472962.557847470170.0932006264663-0.0362087600520.1192652900620.21234853097-0.1098646373710.361724613130.143498591916-0.06414091456040.003611575646750.196649672383-0.05942774834290.06573549961290.2334609241130.0008652261568910.2173520116147.54312448243-14.153774290438.4605732502
60.252877116586-0.225046270731-0.4356647619242.214907948230.1126650379621.034802898630.1916855653790.8219849116560.668916531541-0.3499351098580.4028390913631.073031991760.307244920377-1.183052708110.007647758453830.228365192002-0.0750527262378-0.1304753621710.7114123062240.2808614676370.5044530156989.75122114542-5.1859680410119.2469864673
72.430306600810.6937841163040.2312536156492.17447692808-0.3552912949782.600217669190.05397612526780.2976407203710.361140090354-0.1558271022060.05599833118730.0533586696279-0.1611143459080.028690591722-0.03846322412250.140420675870.01327579440740.03870161421480.2313690438510.06512772063030.23924695360530.7728652334-2.2727911848722.8627777154
86.10774592702-0.478426010787-0.6517030863340.8725146973712.577548964747.62035365625-0.008748388811560.332865475073-0.594581484838-0.4695742090680.3274502823240.8925571924511.21722054298-0.780630013778-0.2720958063070.329879821817-0.0717331506519-0.1270239318180.3955559084660.02054186742890.33284185554825.0416666062-13.466348210815.1235342814
92.35016415407-0.143822645897-0.1474510571322.021931182750.1289915984782.636517350560.1300100719390.124234738759-0.0937396127926-0.0723977726897-0.0445279141129-0.1749720255490.1502922882920.185976363832-0.09785925603060.1187769786730.01015781860920.004266010513280.2111485130890.01698410215860.17548011859838.6683421957-11.21123341225.1476588739
103.841860316950.04673954890151.371978778674.603220219852.006596911243.747142563720.19931851565-0.155851188485-1.016875343621.136549950880.417404016222-0.7479182836540.738927137656-0.240969399831-0.5451731872540.524855452298-0.0117533570504-0.1636070731470.4937486898690.09064307852240.48211353000341.3470682322-18.66989201449.4351400844
Refinement TLS group

Refine-ID: X-RAY DIFFRACTION

IDRefine TLS-IDSelection detailsAuth asym-IDLabel asym-IDAuth seq-IDLabel seq-ID
11chain 'A' and (resid 3 through 16 )AA3 - 161 - 14
22chain 'A' and (resid 17 through 79 )AA17 - 7915 - 77
33chain 'A' and (resid 102 through 119 )AA102 - 11978 - 95
44chain 'A' and (resid 120 through 132 )AA120 - 13296 - 108
55chain 'A' and (resid 133 through 158 )AA133 - 158109 - 134
66chain 'A' and (resid 159 through 195 )AA159 - 195135 - 171
77chain 'B' and (resid 5 through 69 )BB5 - 691 - 65
88chain 'B' and (resid 70 through 107 )BB70 - 10766 - 84
99chain 'B' and (resid 108 through 188 )BB108 - 18885 - 165
1010chain 'B' and (resid 189 through 203 )BB189 - 203166 - 180

+
About Yorodumi

-
News

-
Feb 9, 2022. New format data for meta-information of EMDB entries

New format data for meta-information of EMDB entries

  • Version 3 of the EMDB header file is now the official format.
  • The previous official version 1.9 will be removed from the archive.

Related info.:EMDB header

External links:wwPDB to switch to version 3 of the EMDB data model

-
Aug 12, 2020. Covid-19 info

Covid-19 info

URL: https://pdbj.org/emnavi/covid19.php

New page: Covid-19 featured information page in EM Navigator.

Related info.:Covid-19 info / Mar 5, 2020. Novel coronavirus structure data

+
Mar 5, 2020. Novel coronavirus structure data

Novel coronavirus structure data

Related info.:Yorodumi Speices / Aug 12, 2020. Covid-19 info

External links:COVID-19 featured content - PDBj / Molecule of the Month (242)：Coronavirus Proteases

+
Jan 31, 2019. EMDB accession codes are about to change! (news from PDBe EMDB page)

EMDB accession codes are about to change! (news from PDBe EMDB page)

  • The allocation of 4 digits for EMDB accession codes will soon come to an end. Whilst these codes will remain in use, new EMDB accession codes will include an additional digit and will expand incrementally as the available range of codes is exhausted. The current 4-digit format prefixed with “EMD-” (i.e. EMD-XXXX) will advance to a 5-digit format (i.e. EMD-XXXXX), and so on. It is currently estimated that the 4-digit codes will be depleted around Spring 2019, at which point the 5-digit format will come into force.
  • The EM Navigator/Yorodumi systems omit the EMD- prefix.

Related info.:Q: What is EMD? / ID/Accession-code notation in Yorodumi/EM Navigator

External links:EMDB Accession Codes are Changing Soon! / Contact to PDBj

+
Jul 12, 2017. Major update of PDB

Major update of PDB

  • wwPDB released updated PDB data conforming to the new PDBx/mmCIF dictionary.
  • This is a major update changing the version number from 4 to 5, and with Remediation, in which all the entries are updated.
  • In this update, many items about electron microscopy experimental information are reorganized (e.g. em_software).
  • Now, EM Navigator and Yorodumi are based on the updated data.

External links:wwPDB Remediation / Enriched Model Files Conforming to OneDep Data Standards Now Available in the PDB FTP Archive

-
Yorodumi

Thousand views of thousand structures

  • Yorodumi is a browser for structure data from EMDB, PDB, SASBDB, etc.
  • This page is also the successor to EM Navigator detail page, and also detail information page/front-end page for Omokage search.
  • The word "yorodu" (or yorozu) is an old Japanese word meaning "ten thousand". "mi" (miru) is to see.

Related info.:EMDB / PDB / SASBDB / Comparison of 3 databanks / Yorodumi Search / Aug 31, 2016. New EM Navigator & Yorodumi / Yorodumi Papers / Jmol/JSmol / Function and homology information / Changes in new EM Navigator and Yorodumi

Read more