[English] 日本語
Yorodumi
- PDB-4j5p: Crystal Structure of a Covalently Bound alpha-Ketoheterocycle Inh... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 4j5p
TitleCrystal Structure of a Covalently Bound alpha-Ketoheterocycle Inhibitor (Phenhexyl/Oxadiazole/Pyridine) to a Humanized Variant of Fatty Acid Amide Hydrolase
ComponentsFatty-acid amide hydrolase 1
KeywordsHYDROLASE/HYDROLASE INHIBITOR / HYDROLASE-HYDROLASE INHIBITOR complex
Function / homology
Function and homology information


Arachidonic acid metabolism / fatty acid amide hydrolase / fatty acid amide hydrolase activity / monoacylglycerol catabolic process / monoacylglycerol lipase activity / amidase activity / fatty acid catabolic process / Hydrolases; Acting on ester bonds; Carboxylic-ester hydrolases / hydrolase activity, acting on ester bonds / organelle membrane ...Arachidonic acid metabolism / fatty acid amide hydrolase / fatty acid amide hydrolase activity / monoacylglycerol catabolic process / monoacylglycerol lipase activity / amidase activity / fatty acid catabolic process / Hydrolases; Acting on ester bonds; Carboxylic-ester hydrolases / hydrolase activity, acting on ester bonds / organelle membrane / positive regulation of vasoconstriction / fatty acid metabolic process / phospholipid binding / Golgi membrane / lipid binding / endoplasmic reticulum membrane / identical protein binding
Similarity search - Function
Amidase, conserved site / Amidases signature. / Amidase signature (AS) enzymes / Amidase signature (AS) domain / Amidase signature domain / Amidase signature (AS) superfamily / Amidase / Alpha-Beta Complex / Alpha Beta
Similarity search - Domain/homology
Chem-BR1 / DI(HYDROXYETHYL)ETHER / Fatty-acid amide hydrolase 1
Similarity search - Component
Biological speciesRattus norvegicus (Norway rat)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MIR / Resolution: 2.3 Å
AuthorsOtrubova, K. / Brown, M. / McCormick, M.S. / Han, G.W. / O'Neal, S.T. / Cravatt, B.F. / Stevens, R.C. / Lichtman, A.H. / Boger, D.L.
CitationJournal: J.Am.Chem.Soc. / Year: 2013
Title: Rational design of Fatty Acid amide hydrolase inhibitors that act by covalently bonding to two active site residues.
Authors: Otrubova, K. / Brown, M. / McCormick, M.S. / Han, G.W. / O'Neal, S.T. / Cravatt, B.F. / Stevens, R.C. / Lichtman, A.H. / Boger, D.L.
History
DepositionFeb 8, 2013Deposition site: RCSB / Processing site: RCSB
Revision 1.0May 1, 2013Provider: repository / Type: Initial release
Revision 1.1May 8, 2013Group: Database references
Revision 1.2Nov 15, 2017Group: Refinement description / Category: software / Item: _software.name
Revision 1.3Sep 20, 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 / struct_ncs_dom_lim / struct_ref_seq_dif / struct_site
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.pdbx_leaving_atom_flag / _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_label_asym_id / _struct_conn.ptnr2_label_atom_id / _struct_ncs_dom_lim.beg_auth_comp_id / _struct_ncs_dom_lim.beg_label_asym_id / _struct_ncs_dom_lim.beg_label_comp_id / _struct_ncs_dom_lim.beg_label_seq_id / _struct_ncs_dom_lim.end_auth_comp_id / _struct_ncs_dom_lim.end_label_asym_id / _struct_ncs_dom_lim.end_label_comp_id / _struct_ncs_dom_lim.end_label_seq_id / _struct_ref_seq_dif.details / _struct_site.pdbx_auth_asym_id / _struct_site.pdbx_auth_comp_id / _struct_site.pdbx_auth_seq_id

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Fatty-acid amide hydrolase 1
B: Fatty-acid amide hydrolase 1
hetero molecules


Theoretical massNumber of molelcules
Total (without water)127,64810
Polymers126,2232
Non-polymers1,4258
Water5,296294
1


  • Idetical with deposited unit
  • defined by author&software
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area4480 Å2
ΔGint-15 kcal/mol
Surface area37290 Å2
MethodPISA
Unit cell
Length a, b, c (Å)104.067, 104.067, 261.034
Angle α, β, γ (deg.)90.00, 90.00, 120.00
Int Tables number154
Space group name H-MP3221
Noncrystallographic symmetry (NCS)NCS domain:
IDEns-IDDetails
11A
21B

NCS domain segments:

Component-ID: _ / Ens-ID: 1 / Beg auth comp-ID: GLY / Beg label comp-ID: GLY / End auth comp-ID: GLN / End label comp-ID: GLN / Refine code: _ / Auth seq-ID: 33 - 575 / Label seq-ID: 27 - 569

Dom-IDAuth asym-IDLabel asym-ID
1AA
2BB

-
Components

#1: Protein Fatty-acid amide hydrolase 1 / Anandamide amidohydrolase 1 / Oleamide hydrolase 1


Mass: 63111.664 Da / Num. of mol.: 2 / Fragment: deltaTM-FAAH (UNP residues 30-579) / Mutation: L192F, F194Y, A377T, S435N, I491V, V495M
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Rattus norvegicus (Norway rat) / Gene: Faah, Faah1 / Plasmid: pET28a / Production host: Escherichia coli (E. coli) / Strain (production host): BL21 / References: UniProt: P97612, fatty acid amide hydrolase
#2: Chemical ChemComp-BR1 / (1S)-1-{5-[5-(bromomethyl)pyridin-2-yl]-1,3-oxazol-2-yl}-7-phenylheptan-1-ol / 1-(5-(5-(bromomethyl)pyridin-2-yl)-7-phenylheptan-1-one, bound form


Mass: 429.350 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C22H25BrN2O2
#3: Chemical
ChemComp-PEG / DI(HYDROXYETHYL)ETHER


Mass: 106.120 Da / Num. of mol.: 5 / Source method: obtained synthetically / Formula: C4H10O3
#4: Chemical ChemComp-CL / CHLORIDE ION


Mass: 35.453 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: Cl
#5: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 294 / 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: 3.23 Å3/Da / Density % sol: 61.95 %
Crystal growTemperature: 287 K / Method: vapor diffusion, sitting drop / pH: 5.5
Details: 50 mM MES, pH 5.5, 0.02% UM-LA, 15% PEG400, 4% polypropylene glycol P400, 13% xylitol, 1 mM DTT, 50 mM potassium chloride, 50 mM sodium fluoride, VAPOR DIFFUSION, SITTING DROP, temperature 287K

-
Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: SYNCHROTRON / Site: SSRL / Beamline: BL11-1 / Wavelength: 0.979 Å
DetectorType: DECTRIS PILATUS 6M / Detector: PIXEL / Date: Jan 19, 2011
RadiationMonochromator: Side scattering bent cube-root I-beam single crystal, asymmetric cut 4.965 degrees
Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.979 Å / Relative weight: 1
ReflectionResolution: 2.3→50 Å / Num. obs: 71819 / % possible obs: 97.4 % / Redundancy: 6.4 % / Rsym value: 0.127 / Net I/σ(I): 11.8
Reflection shellResolution: 2.3→2.38 Å / Redundancy: 2.8 % / Rmerge(I) obs: 0.9 / Mean I/σ(I) obs: 1.2 / Num. unique all: 6384 / % possible all: 88

-
Processing

Software
NameVersionClassification
Blu-Icedata collection
PHASERphasing
REFMAC5.7.0029refinement
HKL-2000data reduction
HKL-2000data scaling
RefinementMethod to determine structure: MIR
Starting model: PDB ENTRY 3K84

3k84


Resolution: 2.3→33.38 Å / Cor.coef. Fo:Fc: 0.955 / Cor.coef. Fo:Fc free: 0.939 / SU B: 17.438 / SU ML: 0.196 / Cross valid method: THROUGHOUT / ESU R: 0.269 / ESU R Free: 0.225 / Stereochemistry target values: MAXIMUM LIKELIHOOD
Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS U VALUES : RESIDUAL ONLY
RfactorNum. reflection% reflectionSelection details
Rfree0.26487 3602 5 %RANDOM
Rwork0.2199 ---
obs0.22216 68002 97.22 %-
all-71819 --
Solvent computationIon probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å / Solvent model: MASK
Displacement parametersBiso mean: 61.639 Å2
Baniso -1Baniso -2Baniso -3
1--0.08 Å2-0.08 Å20 Å2
2---0.08 Å20 Å2
3---0.26 Å2
Refinement stepCycle: LAST / Resolution: 2.3→33.38 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms8405 0 88 294 8787
Refine LS restraints
Refine-IDTypeDev idealDev ideal targetNumber
X-RAY DIFFRACTIONr_bond_refined_d0.0160.0198683
X-RAY DIFFRACTIONr_bond_other_d0.0060.028435
X-RAY DIFFRACTIONr_angle_refined_deg1.764211765
X-RAY DIFFRACTIONr_angle_other_deg1.2013.00219455
X-RAY DIFFRACTIONr_dihedral_angle_1_deg6.02751087
X-RAY DIFFRACTIONr_dihedral_angle_2_deg39.04323.855345
X-RAY DIFFRACTIONr_dihedral_angle_3_deg17.76151480
X-RAY DIFFRACTIONr_dihedral_angle_4_deg22.2791556
X-RAY DIFFRACTIONr_chiral_restr0.0950.21309
X-RAY DIFFRACTIONr_gen_planes_refined0.0090.0219711
X-RAY DIFFRACTIONr_gen_planes_other0.0050.021907
Refine LS restraints NCS

Ens-ID: 1 / Number: 34736 / Refine-ID: X-RAY DIFFRACTION / Type: interatomic distance / Rms dev position: 0.08 Å / Weight position: 0.05

Dom-IDAuth asym-ID
1A
2B
LS refinement shellResolution: 2.3→2.36 Å / Total num. of bins used: 20
RfactorNum. reflection% reflection
Rfree0.574 260 -
Rwork0.554 4344 -
obs--86.2 %
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)
11.1053-0.2871-0.32090.95790.13871.0887-0.05570.3007-0.0405-0.0984-0.0108-0.03890.2207-0.05470.06650.346-0.25390.07940.3154-0.06630.020357.8075-22.396-35.7267
20.65930.1483-0.16021.47350.56551.2440.1439-0.03110.10780.4188-0.12060.02120.07970.0531-0.02330.5003-0.31440.10430.2415-0.06710.036255.0827-5.04332.7289
Refinement TLS group
IDRefine-IDRefine TLS-IDAuth asym-IDAuth seq-ID
1X-RAY DIFFRACTION1A33 - 576
2X-RAY DIFFRACTION2B33 - 577

+
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://pdbjlvh1.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