[English] 日本語
Yorodumi
- PDB-5ji6: Potent, Reversible MetAP2 Inhibitors via FBDD -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 5ji6
TitlePotent, Reversible MetAP2 Inhibitors via FBDD
ComponentsMethionine aminopeptidase 2Methionyl aminopeptidase
KeywordsHydrolase4/Hydrolase Inhibitor / Hydrolase / peptidase / metal ion binding / proteolysis / Hydrolase4-Hydrolase Inhibitor complex
Function / homology
Function and homology information


N-terminal protein amino acid modification / peptidyl-methionine modification / initiator methionyl aminopeptidase activity / methionyl aminopeptidase / metalloexopeptidase activity / metalloaminopeptidase activity / aminopeptidase activity / protein processing / Inactivation, recovery and regulation of the phototransduction cascade / RNA binding ...N-terminal protein amino acid modification / peptidyl-methionine modification / initiator methionyl aminopeptidase activity / methionyl aminopeptidase / metalloexopeptidase activity / metalloaminopeptidase activity / aminopeptidase activity / protein processing / Inactivation, recovery and regulation of the phototransduction cascade / RNA binding / metal ion binding / plasma membrane / cytosol / cytoplasm
Similarity search - Function
Peptidase M24A, methionine aminopeptidase, subfamily 2 / Peptidase M24A, methionine aminopeptidase, subfamily 2, binding site / Methionine aminopeptidase subfamily 2 signature. / Peptidase M24, methionine aminopeptidase / Creatine Amidinohydrolase / Creatinase/methionine aminopeptidase superfamily / Peptidase M24 / Metallopeptidase family M24 / Creatinase/aminopeptidase-like / Winged helix-like DNA-binding domain superfamily/Winged helix DNA-binding domain ...Peptidase M24A, methionine aminopeptidase, subfamily 2 / Peptidase M24A, methionine aminopeptidase, subfamily 2, binding site / Methionine aminopeptidase subfamily 2 signature. / Peptidase M24, methionine aminopeptidase / Creatine Amidinohydrolase / Creatinase/methionine aminopeptidase superfamily / Peptidase M24 / Metallopeptidase family M24 / Creatinase/aminopeptidase-like / Winged helix-like DNA-binding domain superfamily/Winged helix DNA-binding domain / Arc Repressor Mutant, subunit A / Winged helix DNA-binding domain superfamily / Winged helix-like DNA-binding domain superfamily / Alpha-Beta Complex / Orthogonal Bundle / Mainly Alpha / Alpha Beta
Similarity search - Domain/homology
Chem-6KN / : / Methionine aminopeptidase 2
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.15 Å
AuthorsDougan, D.R. / Lawson, J.D.
CitationJournal: Bioorg.Med.Chem.Lett. / Year: 2016
Title: Discovery of potent, reversible MetAP2 inhibitors via fragment based drug discovery and structure based drug design-Part 1.
Authors: Cheruvallath, Z. / Tang, M. / McBride, C. / Komandla, M. / Miura, J. / Ton-Nu, T. / Erikson, P. / Feng, J. / Farrell, P. / Lawson, J.D. / Vanderpool, D. / Wu, Y. / Dougan, D.R. / Plonowski, ...Authors: Cheruvallath, Z. / Tang, M. / McBride, C. / Komandla, M. / Miura, J. / Ton-Nu, T. / Erikson, P. / Feng, J. / Farrell, P. / Lawson, J.D. / Vanderpool, D. / Wu, Y. / Dougan, D.R. / Plonowski, A. / Holub, C. / Larson, C.
History
DepositionApr 21, 2016Deposition site: RCSB / Processing site: RCSB
Revision 1.0May 25, 2016Provider: repository / Type: Initial release
Revision 1.1Jun 15, 2016Group: Database references
Revision 1.2Nov 22, 2017Group: Database references / Derived calculations / Refinement description
Category: citation / pdbx_struct_oper_list / software
Item: _citation.journal_id_CSD / _pdbx_struct_oper_list.symmetry_operation / _software.classification

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Methionine aminopeptidase 2
hetero molecules


Theoretical massNumber of molelcules
Total (without water)41,8395
Polymers41,3561
Non-polymers4834
Water2,378132
1


  • Idetical with deposited unit
  • defined by author&software
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
Unit cell
Length a, b, c (Å)88.962, 100.100, 99.469
Angle α, β, γ (deg.)90.000, 90.000, 90.000
Int Tables number20
Space group name H-MC2221

-
Components

#1: Protein Methionine aminopeptidase 2 / Methionyl aminopeptidase / MetAP 2 / Initiation factor 2-associated 67 kDa glycoprotein / p67eIF2 / Peptidase M


Mass: 41355.977 Da / Num. of mol.: 1 / Fragment: UNP residues 87-455
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: METAP2, MNPEP, P67EIF2 / Production host: Spodoptera frugiperda (fall armyworm) / Strain (production host): sf9 / References: UniProt: P50579, methionyl aminopeptidase
#2: Chemical ChemComp-MN / MANGANESE (II) ION


Mass: 54.938 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: Mn
#3: Chemical ChemComp-SO4 / SULFATE ION / Sulfate


Mass: 96.063 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: SO4
#4: Chemical ChemComp-6KN / 4-(3-methylpyridin-4-yl)-6-(trifluoromethyl)-1H-indazole


Mass: 277.245 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C14H10F3N3
#5: Water ChemComp-HOH / water / Water


Mass: 18.015 Da / Num. of mol.: 132 / 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: 2.68 Å3/Da / Density % sol: 54.06 %
Crystal growTemperature: 293 K / Method: vapor diffusion, sitting drop / pH: 5.9
Details: 24.% PEG MME 2000, 0.05M MES pH 5.9, 0.0175M Ammonium Sulfate

-
Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: SYNCHROTRON / Site: SSRL / Beamline: BL9-2 / Wavelength: 0.9765 Å
DetectorType: MARMOSAIC 325 mm CCD / Detector: CCD / Date: Apr 19, 2012
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.9765 Å / Relative weight: 1
ReflectionResolution: 2.15→50 Å / Num. obs: 24715 / % possible obs: 99.8 % / Redundancy: 5.5 % / Rmerge(I) obs: 0.076 / Χ2: 1.071 / Net I/av σ(I): 23.083 / Net I/σ(I): 8.1 / Num. measured all: 135595
Reflection shell
Resolution (Å)Redundancy (%)Rmerge(I) obsDiffraction-ID% possible all
2.15-2.194.90.916198.9
2.19-2.235.20.784199.8
2.23-2.275.40.7481100
2.27-2.325.50.6221100
2.32-2.375.60.6031100
2.37-2.425.60.5051100
2.42-2.485.60.4711100
2.48-2.555.60.3711100
2.55-2.625.60.2951100
2.62-2.715.60.2761100
2.71-2.815.50.2341100
2.81-2.925.60.1641100
2.92-3.055.60.131100
3.05-3.215.60.0931100
3.21-3.415.60.0711100
3.41-3.685.60.053199.9
3.68-4.055.50.043199.8
4.05-4.635.50.034199.8
4.63-5.835.50.033199.7
5.83-505.20.028198.6

-
Processing

Software
NameVersionClassification
REFMAC5.7.0025refinement
HKL-2000data scaling
PDB_EXTRACT3.2data extraction
XFITdata reduction
RefinementMethod to determine structure: MOLECULAR REPLACEMENT / Resolution: 2.15→30 Å / Cor.coef. Fo:Fc: 0.969 / Cor.coef. Fo:Fc free: 0.951 / SU B: 12.023 / SU ML: 0.154 / Cross valid method: THROUGHOUT / σ(F): 0 / ESU R: 0.21 / ESU R Free: 0.182
Details: HYDROGENS HAVE BEEN USED IF PRESENT IN THE INPUT U VALUES : WITH TLS ADDED
RfactorNum. reflection% reflectionSelection details
Rfree0.2297 1250 5.1 %RANDOM
Rwork0.1821 ---
obs0.1844 23252 99.89 %-
Solvent computationIon probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å
Displacement parametersBiso max: 147.27 Å2 / Biso mean: 54.495 Å2 / Biso min: 23.89 Å2
Baniso -1Baniso -2Baniso -3
1-3.87 Å20 Å20 Å2
2---3.85 Å20 Å2
3----0.02 Å2
Refinement stepCycle: final / Resolution: 2.15→30 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms2890 0 27 132 3049
Biso mean--68.57 53.17 -
Num. residues----368
Refine LS restraints
Refine-IDTypeDev idealDev ideal targetNumber
X-RAY DIFFRACTIONr_bond_refined_d0.0080.0192985
X-RAY DIFFRACTIONr_angle_refined_deg1.1781.9724048
X-RAY DIFFRACTIONr_dihedral_angle_1_deg5.8425368
X-RAY DIFFRACTIONr_dihedral_angle_2_deg34.13924.412136
X-RAY DIFFRACTIONr_dihedral_angle_3_deg14.46315516
X-RAY DIFFRACTIONr_dihedral_angle_4_deg12.131518
X-RAY DIFFRACTIONr_chiral_restr0.0790.2442
X-RAY DIFFRACTIONr_gen_planes_refined0.0040.0212272
LS refinement shellResolution: 2.15→2.206 Å / Total num. of bins used: 20
RfactorNum. reflection% reflection
Rfree0.378 115 -
Rwork0.29 1660 -
all-1775 -
obs--99.61 %
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)
13.0571-0.2261-0.08753.3868-0.51911.5589-0.0817-0.2263-0.6708-1.2493-0.07290.59260.60870.08610.15450.59250.0368-0.11750.12590.00040.28919.893212.20141.9128
20.3480.4219-0.6113.2136-0.50741.1293-0.19080.07120.0376-0.82580.21440.64440.387-0.0588-0.02360.34220.0041-0.19380.1259-0.03660.178221.577917.07292.7056
30.5219-0.04720.38873.703-0.61041.60980.08680.0150.0203-0.1043-0.03310.09430.03050.0983-0.05380.0190.00160.00470.1004-0.01490.023730.657628.670514.0506
40.6491-0.10490.29643.3976-0.331.9017-0.0056-0.1275-0.13380.27680.09840.99760.1988-0.3178-0.09280.13-0.06970.05410.14840.04110.337516.94513.243723.488
50.6637-0.1030.97692.8782-0.93893.51410.0264-0.1641-0.01650.40610.09921.09490.0437-0.5316-0.12560.1297-0.02690.13640.16770.03330.461414.88521.281622.8952
60.0743-0.49430.03373.7707-1.2872.7664-0.0263-0.0013-0.13670.31490.19280.9857-0.3254-0.2826-0.16650.04730.03220.07110.13810.01540.305416.957141.490915.0949
70.2176-1.0090.00245.0454-0.42142.38980.1108-0.0202-0.0761-0.24280.13040.6033-0.3473-0.1701-0.24130.18740.02160.03440.1212-0.00120.236320.488647.95065.7046
80.3145-0.29150.23823.2962-0.72491.4970.0962-0.0205-0.00130.04610.02330.6264-0.0116-0.1259-0.11940.0389-0.01040.02810.0938-0.00480.140222.219431.663914.8877
Refinement TLS group
IDRefine-IDRefine TLS-IDAuth asym-IDAuth seq-ID
1X-RAY DIFFRACTION1A110 - 149
2X-RAY DIFFRACTION2A150 - 189
3X-RAY DIFFRACTION3A190 - 269
4X-RAY DIFFRACTION4A270 - 309
5X-RAY DIFFRACTION5A310 - 374
6X-RAY DIFFRACTION6A375 - 394
7X-RAY DIFFRACTION7A395 - 414
8X-RAY DIFFRACTION8A415 - 478

+
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