[English] 日本語
Yorodumi
- PDB-4zx9: X-ray crystal structure of PfA-M17 in complex with hydroxamic aci... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 4zx9
TitleX-ray crystal structure of PfA-M17 in complex with hydroxamic acid-based inhibitor 10b
ComponentsProbable M17 family aminopeptidase
KeywordsHYDROLASE/HYDROLASE INHIBITOR / M17 LEUCYL-AMINOPEPTIDASE / PROTEASE / INHIBITOR / HYDROXAMIC ACID / HYDROLASE-HYDROLASE INHIBITOR complex
Function / homology
Function and homology information


leucyl aminopeptidase / metalloaminopeptidase activity / manganese ion binding / proteolysis / cytoplasm
Similarity search - Function
Peptidase M17, leucine aminopeptidase / Cytosol aminopeptidase signature. / Peptidase M17, leucyl aminopeptidase, C-terminal / Peptidase M17, leucine aminopeptidase/peptidase B / Cytosol aminopeptidase family, catalytic domain / Leucine Aminopeptidase, subunit E, domain 1 / Leucine Aminopeptidase, subunit E; domain 1 / Zn peptidases / Aminopeptidase / Macro domain-like ...Peptidase M17, leucine aminopeptidase / Cytosol aminopeptidase signature. / Peptidase M17, leucyl aminopeptidase, C-terminal / Peptidase M17, leucine aminopeptidase/peptidase B / Cytosol aminopeptidase family, catalytic domain / Leucine Aminopeptidase, subunit E, domain 1 / Leucine Aminopeptidase, subunit E; domain 1 / Zn peptidases / Aminopeptidase / Macro domain-like / 3-Layer(aba) Sandwich / Alpha Beta
Similarity search - Domain/homology
Chem-4TK / CARBONATE ION / leucyl aminopeptidase
Similarity search - Component
Biological speciesPlasmodium falciparum FcB1/Columbia (eukaryote)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.6 Å
AuthorsDrinkwater, N. / McGowan, S.
Funding support Australia, 1items
OrganizationGrant numberCountry
National Health and Medical Research Council (NHMRC, Australia)1063786 Australia
CitationJournal: Eur.J.Med.Chem. / Year: 2016
Title: Potent dual inhibitors of Plasmodium falciparum M1 and M17 aminopeptidases through optimization of S1 pocket interactions.
Authors: Drinkwater, N. / Vinh, N.B. / Mistry, S.N. / Bamert, R.S. / Ruggeri, C. / Holleran, J.P. / Loganathan, S. / Paiardini, A. / Charman, S.A. / Powell, A.K. / Avery, V.M. / McGowan, S. / Scammells, P.J.
History
DepositionMay 20, 2015Deposition site: RCSB / Processing site: RCSB
Revision 1.0Mar 30, 2016Provider: repository / Type: Initial release
Revision 1.1Sep 27, 2017Group: Author supporting evidence / Data collection ...Author supporting evidence / Data collection / Database references / Derived calculations
Category: citation / diffrn_source ...citation / diffrn_source / pdbx_audit_support / pdbx_struct_oper_list
Item: _citation.journal_id_CSD / _diffrn_source.pdbx_synchrotron_site ..._citation.journal_id_CSD / _diffrn_source.pdbx_synchrotron_site / _pdbx_audit_support.funding_organization / _pdbx_struct_oper_list.symmetry_operation
Revision 1.2Jan 8, 2020Group: Author supporting evidence / Category: pdbx_audit_support / Item: _pdbx_audit_support.funding_organization
Revision 1.3Sep 27, 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 / struct_conn
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession ..._database_2.pdbx_DOI / _database_2.pdbx_database_accession / _struct_conn.pdbx_dist_value / _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

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Probable M17 family aminopeptidase
B: Probable M17 family aminopeptidase
C: Probable M17 family aminopeptidase
D: Probable M17 family aminopeptidase
E: Probable M17 family aminopeptidase
F: Probable M17 family aminopeptidase
G: Probable M17 family aminopeptidase
H: Probable M17 family aminopeptidase
I: Probable M17 family aminopeptidase
J: Probable M17 family aminopeptidase
K: Probable M17 family aminopeptidase
L: Probable M17 family aminopeptidase
hetero molecules


Theoretical massNumber of molelcules
Total (without water)708,700101
Polymers695,78712
Non-polymers12,91489
Water23,5101305
1
A: Probable M17 family aminopeptidase
B: Probable M17 family aminopeptidase
C: Probable M17 family aminopeptidase
D: Probable M17 family aminopeptidase
E: Probable M17 family aminopeptidase
F: Probable M17 family aminopeptidase
hetero molecules


Theoretical massNumber of molelcules
Total (without water)354,02547
Polymers347,8936
Non-polymers6,13241
Water1086
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area27560 Å2
ΔGint-133 kcal/mol
Surface area95260 Å2
MethodPISA
2
G: Probable M17 family aminopeptidase
H: Probable M17 family aminopeptidase
I: Probable M17 family aminopeptidase
J: Probable M17 family aminopeptidase
K: Probable M17 family aminopeptidase
L: Probable M17 family aminopeptidase
hetero molecules


Theoretical massNumber of molelcules
Total (without water)354,67554
Polymers347,8936
Non-polymers6,78248
Water1086
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area27890 Å2
ΔGint-130 kcal/mol
Surface area95350 Å2
MethodPISA
Unit cell
Length a, b, c (Å)173.849, 176.970, 229.862
Angle α, β, γ (deg.)90.000, 90.000, 90.000
Int Tables number19
Space group name H-MP212121

-
Components

-
Protein , 1 types, 12 molecules ABCDEFGHIJKL

#1: Protein
Probable M17 family aminopeptidase


Mass: 57982.230 Da / Num. of mol.: 12 / Fragment: UNP residues 84-605 / Mutation: D152N,D515N,D516N
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Plasmodium falciparum FcB1/Columbia (eukaryote)
Strain: isolate FcB1 / Columbia / Plasmid: PTRCHIS-2B / Production host: Escherichia coli (E. coli) / Strain (production host): BL21 / References: UniProt: A0A024V0B1, leucyl aminopeptidase

-
Non-polymers , 8 types, 1394 molecules

#2: Chemical
ChemComp-4TK / N-[(1R)-1-(4-bromophenyl)-2-(hydroxyamino)-2-oxoethyl]-2,2-dimethylpropanamide


Mass: 329.190 Da / Num. of mol.: 12 / Source method: obtained synthetically / Formula: C13H17BrN2O3
#3: Chemical...
ChemComp-ZN / ZINC ION


Mass: 65.409 Da / Num. of mol.: 24 / Source method: obtained synthetically / Formula: Zn
#4: Chemical
ChemComp-CO3 / CARBONATE ION


Mass: 60.009 Da / Num. of mol.: 12 / Source method: obtained synthetically / Formula: CO3
#5: Chemical
ChemComp-GOL / GLYCEROL / GLYCERIN / PROPANE-1,2,3-TRIOL


Mass: 92.094 Da / Num. of mol.: 5 / Source method: obtained synthetically / Formula: C3H8O3
#6: Chemical
ChemComp-1PE / PENTAETHYLENE GLYCOL / PEG400


Mass: 238.278 Da / Num. of mol.: 20 / Source method: obtained synthetically / Formula: C10H22O6 / Comment: precipitant*YM
#7: Chemical
ChemComp-SO4 / SULFATE ION


Mass: 96.063 Da / Num. of mol.: 11 / Source method: obtained synthetically / Formula: SO4
#8: Chemical
ChemComp-DMS / DIMETHYL SULFOXIDE


Mass: 78.133 Da / Num. of mol.: 5 / Source method: obtained synthetically / Formula: C2H6OS / Comment: DMSO, precipitant*YM
#9: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 1305 / 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: 2.56 Å3/Da / Density % sol: 51.94 %
Crystal growTemperature: 298 K / Method: vapor diffusion, hanging drop / pH: 8.5 / Details: 40% (v/v) PEG 400, 0.1 M Tris pH 8.5, 0.2 M Li2SO4

-
Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: SYNCHROTRON / Site: Australian Synchrotron / Beamline: MX2 / Wavelength: 0.9537 Å
DetectorType: ADSC QUANTUM 315r / Detector: CCD / Date: Oct 17, 2014
RadiationMonochromator: DOUBLE CRYSTAL SILICON 111 / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.9537 Å / Relative weight: 1
ReflectionResolution: 2.6→48.48 Å / Num. obs: 195787 / % possible obs: 90.7 % / Redundancy: 7.7 % / Biso Wilson estimate: 28.44 Å2 / CC1/2: 0.983 / Rmerge(I) obs: 0.284 / Rpim(I) all: 0.097 / Net I/σ(I): 5.4 / Num. measured all: 1499465 / Scaling rejects: 1011
Reflection shell

Diffraction-ID: 1 / Rejects: _

Resolution (Å)Redundancy (%)Rmerge(I) obsMean I/σ(I) obsNum. measured allNum. unique allCC1/2Rpim(I) all% possible all
2.6-2.647.51.4261.47427299080.5350.50493.1
14.24-48.487.80.05312.4917911830.9980.01981.6

-
Processing

Software
NameVersionClassification
PHENIX1.8.4_1496refinement
Blu-Icedata collection
MOSFLMdata reduction
PHASERphasing
Aimlessdata scaling
PDB_EXTRACT3.15data extraction
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 3KQZ

3kqz


Resolution: 2.6→46.742 Å / FOM work R set: 0.739 / SU ML: 0.39 / Cross valid method: FREE R-VALUE / σ(F): 1.34 / Phase error: 32.45 / Stereochemistry target values: ML
RfactorNum. reflection% reflection
Rfree0.2666 9738 4.99 %
Rwork0.2205 185535 -
obs0.2228 195273 89.97 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL
Displacement parametersBiso max: 98.54 Å2 / Biso mean: 32.61 Å2 / Biso min: 8.7 Å2
Refinement stepCycle: final / Resolution: 2.6→46.742 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms46800 0 605 1305 48710
Biso mean--35.46 30.11 -
Num. residues----6170
Refine LS restraints
Refine-IDTypeDev idealNumber
X-RAY DIFFRACTIONf_bond_d0.00248250
X-RAY DIFFRACTIONf_angle_d0.58565446
X-RAY DIFFRACTIONf_chiral_restr0.0237538
X-RAY DIFFRACTIONf_plane_restr0.0028290
X-RAY DIFFRACTIONf_dihedral_angle_d11.87217133
LS refinement shell

Refine-ID: X-RAY DIFFRACTION / Total num. of bins used: 30

Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkNum. reflection all% reflection obs (%)
2.6-2.62950.40023630.3296243660692
2.6295-2.66050.43083160.32746314663093
2.6605-2.69290.38333410.32036280662192
2.6929-2.7270.34623060.31746354666092
2.727-2.76290.36653150.3066293660892
2.7629-2.80070.36923150.30436285660092
2.8007-2.84070.34253260.29586277660392
2.8407-2.88310.33213300.29126299662992
2.8831-2.92820.31093320.28196230656292
2.9282-2.97620.313260.27876278660492
2.9762-3.02750.34223250.27326286661192
3.0275-3.08250.3152960.2686263655992
3.0825-3.14180.33573490.27386227657691
3.1418-3.20590.33233410.25556208654991
3.2059-3.27560.31463040.24626267657191
3.2756-3.35180.31073150.22956233654891
3.3518-3.43560.27783130.22676164647790
3.4356-3.52840.28163880.22646129651790
3.5284-3.63220.26163220.21396163648590
3.6322-3.74940.2532870.20186197648490
3.7494-3.88340.22023160.18516147646389
3.8834-4.03880.20433180.17916131644989
4.0388-4.22250.22913390.16686104644389
4.2225-4.44490.20053460.15336070641688
4.4449-4.72320.19523470.15436015636288
4.7232-5.08740.19152950.15786120641588
5.0874-5.59860.21912740.17136057633187
5.5986-6.4070.20883420.18446031637387
6.407-8.06540.1993370.16866000633786
8.0654-46.74930.18893140.16855870618481

+
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