[English] 日本語
Yorodumi
- PDB-4zz3: Human GAR transformylase in complex with GAR and pemetrexed -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 4zz3
TitleHuman GAR transformylase in complex with GAR and pemetrexed
ComponentsTrifunctional purine biosynthetic protein adenosine-3
Keywordstransferase/transferase inhibitor / gar transformylase / antifolate / transferase-transferase inhibitor complex
Function / homology
Function and homology information


phosphoribosylformylglycinamidine cyclo-ligase / phosphoribosylformylglycinamidine cyclo-ligase activity / adenine biosynthetic process / phosphoribosylamine-glycine ligase / phosphoribosylamine-glycine ligase activity / phosphoribosylglycinamide formyltransferase 1 / purine ribonucleoside monophosphate biosynthetic process / phosphoribosylglycinamide formyltransferase activity / 'de novo' XMP biosynthetic process / brainstem development ...phosphoribosylformylglycinamidine cyclo-ligase / phosphoribosylformylglycinamidine cyclo-ligase activity / adenine biosynthetic process / phosphoribosylamine-glycine ligase / phosphoribosylamine-glycine ligase activity / phosphoribosylglycinamide formyltransferase 1 / purine ribonucleoside monophosphate biosynthetic process / phosphoribosylglycinamide formyltransferase activity / 'de novo' XMP biosynthetic process / brainstem development / Purine ribonucleoside monophosphate biosynthesis / glycine metabolic process / 'de novo' AMP biosynthetic process / purine nucleotide biosynthetic process / GMP biosynthetic process / 'de novo' IMP biosynthetic process / tetrahydrofolate biosynthetic process / cerebellum development / cerebral cortex development / extracellular exosome / ATP binding / metal ion binding / cytosol
Similarity search - Function
Phosphoribosylformylglycinamidine cyclo-ligase / Phosphoribosylglycinamide synthetase / Phosphoribosylglycinamide synthetase, conserved site / Phosphoribosylglycinamide synthetase, C-domain / Phosphoribosylglycinamide synthetase, N-terminal / Phosphoribosylglycinamide synthetase, C-domain superfamily / Phosphoribosylglycinamide synthetase, C domain / Phosphoribosylglycinamide synthetase, N domain / Phosphoribosylglycinamide synthetase signature. / Phosphoribosylglycinamide synthetase, C domain ...Phosphoribosylformylglycinamidine cyclo-ligase / Phosphoribosylglycinamide synthetase / Phosphoribosylglycinamide synthetase, conserved site / Phosphoribosylglycinamide synthetase, C-domain / Phosphoribosylglycinamide synthetase, N-terminal / Phosphoribosylglycinamide synthetase, C-domain superfamily / Phosphoribosylglycinamide synthetase, C domain / Phosphoribosylglycinamide synthetase, N domain / Phosphoribosylglycinamide synthetase signature. / Phosphoribosylglycinamide synthetase, C domain / Phosphoribosylglycinamide synthetase, ATP-grasp (A) domain / Phosphoribosylglycinamide synthetase, ATP-grasp (A) domain / Phosphoribosylglycinamide formyltransferase / Phosphoribosylglycinamide synthetase, ATP-grasp (A) domain / Formyl transferase, N-terminal domain / PurM-like, N-terminal domain / AIR synthase related protein, N-terminal domain / Phosphoribosylglycinamide formyltransferase, active site / Phosphoribosylglycinamide formyltransferase active site. / PurM-like, C-terminal domain / PurM-like, C-terminal domain superfamily / PurM-like, N-terminal domain superfamily / AIR synthase related protein, C-terminal domain / Formyl transferase, N-terminal / Formyl transferase / Formyl transferase, N-terminal domain superfamily / Rudiment single hybrid motif / ATP-grasp fold, subdomain 1 / Pre-ATP-grasp domain superfamily / ATP-grasp fold / ATP-grasp fold profile. / Rossmann fold / 3-Layer(aba) Sandwich / Alpha Beta
Similarity search - Domain/homology
Chem-4DW / GLYCINAMIDE RIBONUCLEOTIDE / Trifunctional purine biosynthetic protein adenosine-3
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / molecular replacement / Resolution: 2.504 Å
AuthorsDeis, S.M. / Dann III, C.E.
Funding support United States, 2items
OrganizationGrant numberCountry
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)GM094472 United States
National Institutes of Health/National Cancer Institute (NIH/NCI)CA166711 United States
CitationJournal: J.Med.Chem. / Year: 2015
Title: 6-Substituted Pyrrolo[2,3-d]pyrimidine Thienoyl Regioisomers as Targeted Antifolates for Folate Receptor alpha and the Proton-Coupled Folate Transporter in Human Tumors.
Authors: Wang, L. / Wallace, A. / Raghavan, S. / Deis, S.M. / Wilson, M.R. / Yang, S. / Polin, L. / White, K. / Kushner, J. / Orr, S. / George, C. / O'Connor, C. / Hou, Z. / Mitchell-Ryan, S. / Dann, ...Authors: Wang, L. / Wallace, A. / Raghavan, S. / Deis, S.M. / Wilson, M.R. / Yang, S. / Polin, L. / White, K. / Kushner, J. / Orr, S. / George, C. / O'Connor, C. / Hou, Z. / Mitchell-Ryan, S. / Dann, C.E. / Matherly, L.H. / Gangjee, A.
History
DepositionMay 22, 2015Deposition site: RCSB / Processing site: RCSB
Revision 1.0Dec 16, 2015Provider: repository / Type: Initial release
Revision 1.1Sep 20, 2017Group: Author supporting evidence / Database references ...Author supporting evidence / Database references / Derived calculations / Refinement description
Category: citation / pdbx_audit_support ...citation / pdbx_audit_support / pdbx_struct_oper_list / software
Item: _citation.journal_id_CSD / _pdbx_audit_support.funding_organization ..._citation.journal_id_CSD / _pdbx_audit_support.funding_organization / _pdbx_struct_oper_list.symmetry_operation / _software.name
Revision 1.2Jun 13, 2018Group: Data collection / Category: diffrn_radiation / Item: _diffrn_radiation.pdbx_diffrn_protocol
Revision 1.3Dec 4, 2019Group: Author supporting evidence / Category: pdbx_audit_support / Item: _pdbx_audit_support.funding_organization
Revision 1.4Sep 27, 2023Group: Data collection / Database references / Refinement description
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / database_2 / pdbx_initial_refinement_model
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Trifunctional purine biosynthetic protein adenosine-3
hetero molecules


Theoretical massNumber of molelcules
Total (without water)23,5203
Polymers22,8101
Non-polymers7102
Water48627
1


  • Idetical with deposited unit
  • defined by author&software
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
Unit cell
Length a, b, c (Å)74.983, 74.983, 100.934
Angle α, β, γ (deg.)90.000, 90.000, 120.000
Int Tables number154
Space group name H-MP3221

-
Components

#1: Protein Trifunctional purine biosynthetic protein adenosine-3


Mass: 22810.139 Da / Num. of mol.: 1 / Fragment: unp residues 808-1010
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: GART, PGFT, PRGS / Plasmid: pET22B / Production host: Escherichia coli (E. coli) / Strain (production host): Rosetta(DE3)pLysS
References: UniProt: P22102, phosphoribosylamine-glycine ligase, phosphoribosylformylglycinamidine cyclo-ligase, phosphoribosylglycinamide formyltransferase 1
#2: Chemical ChemComp-4DW / N-{4-[2-(2-amino-4-oxo-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidin-5-yl)ethyl]benzoyl}-L-glutamic acid / pemetrexed


Mass: 425.395 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C20H19N5O6 / Comment: medication, chemotherapy*YM
#3: Chemical ChemComp-GAR / GLYCINAMIDE RIBONUCLEOTIDE


Mass: 284.160 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C7H13N2O8P
#4: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 27 / Source method: isolated from a natural source / Formula: H2O

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 3.92 Å3/Da / Density % sol: 68.59 %
Crystal growTemperature: 277 K / Method: vapor diffusion, sitting drop / pH: 7.5 / Details: 18 % PEG4000, 2 % PEG400, 0.33 M NaCl

-
Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: SYNCHROTRON / Site: ALS / Beamline: 4.2.2 / Wavelength: 1.0001 Å
DetectorType: RDI CMOS_8M / Detector: CMOS / Date: Jan 28, 2015
RadiationMonochromator: Rosenbaum-Rock Si(111) sagitally focused monochromator
Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1.0001 Å / Relative weight: 1
ReflectionResolution: 2.5→50 Å / Num. obs: 11694 / % possible obs: 99.6 % / Redundancy: 8 % / Biso Wilson estimate: 35.12 Å2 / Rmerge(I) obs: 0.067 / Rpim(I) all: 0.025 / Rrim(I) all: 0.072 / Χ2: 0.998 / Net I/av σ(I): 28.24 / Net I/σ(I): 17.5 / Num. measured all: 93726
Reflection shell

Diffraction-ID: 1 / Rejects: _

Resolution (Å)Redundancy (%)Rmerge(I) obsNum. unique allCC1/2Rpim(I) allRrim(I) allΧ2% possible all
2.5-2.544.90.3565420.9040.1750.3980.77299.4
2.54-2.595.80.3295900.9420.1460.3620.76499.5
2.59-2.646.70.3395660.9550.1390.3680.774100
2.64-2.697.30.3195860.9760.1240.3430.89199.3
2.69-2.757.60.2585620.9810.0970.2760.8999.6
2.75-2.827.80.2255740.9840.0830.240.97399.8
2.82-2.8980.1815910.990.0670.1931.01599.8
2.89-2.968.20.1315690.9940.0480.140.75100
2.96-3.058.50.1185640.9940.0430.1250.79899.1
3.05-3.158.50.0965940.9960.0340.1020.887100
3.15-3.268.40.0835750.9960.030.0890.973100
3.26-3.398.50.0725840.9970.0260.0770.985100
3.39-3.558.60.0655820.9980.0230.071.148100
3.55-3.738.60.065960.9980.0220.0641.139100
3.73-3.978.80.0545820.9980.0190.0581.21199.5
3.97-4.278.70.0545800.9970.0190.0571.12899.5
4.27-4.78.80.0486040.9980.0170.0511.08499.8
4.7-5.388.90.0475970.9980.0170.051.00699.8
5.38-6.788.90.0526100.9980.0180.0551.07199.3
6.78-508.40.0586460.9950.0210.0621.32197.4

-
Phasing

PhasingMethod: molecular replacement

-
Processing

Software
NameVersionClassification
PHENIXphenix.refine 1.9refinement
SCALEPACK2.5.6data scaling
PDB_EXTRACT3.15data extraction
Cootmodel building
PHASERphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 4YKS

4yks
PDB Unreleased entry


Resolution: 2.504→39.848 Å / SU ML: 0.31 / Cross valid method: FREE R-VALUE / σ(F): 1.36 / Phase error: 23.29 / Stereochemistry target values: ML
RfactorNum. reflection% reflection
Rfree0.2433 1158 10.01 %
Rwork0.1955 10416 -
obs0.2002 11574 98.63 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL
Displacement parametersBiso max: 122.71 Å2 / Biso mean: 48.8973 Å2 / Biso min: 13.46 Å2
Refinement stepCycle: final / Resolution: 2.504→39.848 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms1469 0 49 27 1545
Biso mean--62.88 35.58 -
Num. residues----200
Refine LS restraints
Refine-IDTypeDev idealNumber
X-RAY DIFFRACTIONf_bond_d0.0021565
X-RAY DIFFRACTIONf_angle_d0.6952137
X-RAY DIFFRACTIONf_chiral_restr0.023256
X-RAY DIFFRACTIONf_plane_restr0.003276
X-RAY DIFFRACTIONf_dihedral_angle_d16.365556
LS refinement shell

Refine-ID: X-RAY DIFFRACTION / Total num. of bins used: 8

Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkNum. reflection all% reflection obs (%)
2.5037-2.61760.31011340.24551185131991
2.6176-2.75560.30771420.271512761418100
2.7556-2.92820.32061470.249912881435100
2.9282-3.15420.28321410.234213071448100
3.1542-3.47150.26411470.215713121459100
3.4715-3.97340.23191420.180313201462100
3.9734-5.00450.21861510.154213441495100
5.0045-39.85310.17991540.16131384153899
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)
13.03250.00020.7550.84490.98571.35680.33130.4554-0.0976-1.27120.20250.3620.6003-0.5171-0.27380.9405-0.1337-0.21160.4040.10920.315371.622739.099824.0194
29.34662.01745.94876.03833.18998.60640.40170.2535-0.5497-0.3804-0.1649-0.40350.81870.4365-0.07350.5027-0.02790.00430.28350.0910.332482.501942.233225.7072
35.8432-0.7619-1.00633.24960.95393.71390.48940.3454-1.6583-1.045-0.08650.66621.0256-1.4134-0.2380.93-0.2364-0.32880.64490.08590.700365.751633.151323.7765
45.8403-2.0913-0.56673.6453-2.35522.56850.80060.1721-0.2927-1.02920.28470.51210.7951-1.2919-0.55970.4404-0.1612-0.21270.60710.24960.476463.568142.162227.728
52.33871.0396-1.66585.4129-4.13218.0906-0.0155-0.1498-0.3528-0.10550.23380.20460.3637-0.7718-0.23180.1675-0.0469-0.01280.35890.01630.282767.321855.783617.5487
64.34115.4968-1.43077.633-1.08631.26840.42470.60671.2778-0.35710.84010.8644-0.1736-1.955-1.07410.3905-0.0468-0.01530.83790.30490.656560.512953.730925.8044
75.9916-0.5367-1.18652.48591.37635.52120.04340.2646-0.0466-0.1175-0.1394-0.0153-0.46430.42250.16670.1550.0064-0.0180.14150.020.19475.728459.901312.7585
80.603-0.48950.54772.4011-3.27988.35830.01030.0236-0.45190.06330.1114-0.06490.08870.4843-0.05810.1844-0.0514-0.01630.23750.05770.303177.582151.449318.1484
94.15-0.6173.09518.66510.9297.6496-0.8902-1.19960.56791.61260.24671.1426-0.0895-1.31070.48460.46570.02690.09540.60020.02770.423671.300556.766937.3152
Refinement TLS group
IDRefine-IDRefine TLS-IDSelection detailsAuth asym-IDAuth seq-ID
1X-RAY DIFFRACTION1chain 'A' and (resid 808 through 818 )A0
2X-RAY DIFFRACTION2chain 'A' and (resid 819 through 835 )A0
3X-RAY DIFFRACTION3chain 'A' and (resid 836 through 884 )A0
4X-RAY DIFFRACTION4chain 'A' and (resid 885 through 906 )A0
5X-RAY DIFFRACTION5chain 'A' and (resid 907 through 945 )A0
6X-RAY DIFFRACTION6chain 'A' and (resid 946 through 954 )A0
7X-RAY DIFFRACTION7chain 'A' and (resid 955 through 968 )A0
8X-RAY DIFFRACTION8chain 'A' and (resid 969 through 992 )A0
9X-RAY DIFFRACTION9chain 'A' and (resid 993 through 1007 )A0

+
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