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- PDB-5c0n: Development of a monoclonal antibody targeting secreted aP2 to tr... -

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Basic information

Entry
Database: PDB / ID: 5c0n
TitleDevelopment of a monoclonal antibody targeting secreted aP2 to treat diabetes and fatty liver disease
Components
  • Fab CA33 Heavy chain
  • Fab CA33 light chain
  • Fatty acid-binding protein, adipocyte
KeywordsLIPID TRANSPORT / AP2 / FABP4 / Fab / type II diabetes
Function / homology
Function and homology information


Triglyceride catabolism / hormone receptor binding / long-chain fatty acid transmembrane transporter activity / cellular response to lithium ion / long-chain fatty acid binding / white fat cell differentiation / fatty acid transport / long-chain fatty acid transport / brown fat cell differentiation / fatty acid metabolic process ...Triglyceride catabolism / hormone receptor binding / long-chain fatty acid transmembrane transporter activity / cellular response to lithium ion / long-chain fatty acid binding / white fat cell differentiation / fatty acid transport / long-chain fatty acid transport / brown fat cell differentiation / fatty acid metabolic process / cholesterol homeostasis / fatty acid binding / response to bacterium / positive regulation of inflammatory response / cellular response to tumor necrosis factor / positive regulation of cold-induced thermogenesis / negative regulation of DNA-templated transcription / positive regulation of cell population proliferation / nucleoplasm / nucleus / cytosol / cytoplasm
Similarity search - Function
Cytosolic fatty-acid binding proteins signature. / Intracellular lipid binding protein / Cytosolic fatty-acid binding / Calycin beta-barrel core domain / Lipocalin / cytosolic fatty-acid binding protein family / Lipocalin/cytosolic fatty-acid binding domain / Calycin / Lipocalin / Immunoglobulins / Immunoglobulin-like ...Cytosolic fatty-acid binding proteins signature. / Intracellular lipid binding protein / Cytosolic fatty-acid binding / Calycin beta-barrel core domain / Lipocalin / cytosolic fatty-acid binding protein family / Lipocalin/cytosolic fatty-acid binding domain / Calycin / Lipocalin / Immunoglobulins / Immunoglobulin-like / Beta Barrel / Sandwich / Mainly Beta
Similarity search - Domain/homology
Fatty acid-binding protein, adipocyte
Similarity search - Component
Biological speciesMus musculus (house mouse)
Oryctolagus cuniculus (rabbit)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 3 Å
AuthorsDoyle, C.
CitationJournal: Sci Transl Med / Year: 2015
Title: Development of a therapeutic monoclonal antibody that targets secreted fatty acid-binding protein aP2 to treat type 2 diabetes.
Authors: Burak, M.F. / Inouye, K.E. / White, A. / Lee, A. / Tuncman, G. / Calay, E.S. / Sekiya, M. / Tirosh, A. / Eguchi, K. / Birrane, G. / Lightwood, D. / Howells, L. / Odede, G. / Hailu, H. / ...Authors: Burak, M.F. / Inouye, K.E. / White, A. / Lee, A. / Tuncman, G. / Calay, E.S. / Sekiya, M. / Tirosh, A. / Eguchi, K. / Birrane, G. / Lightwood, D. / Howells, L. / Odede, G. / Hailu, H. / West, S. / Garlish, R. / Neale, H. / Doyle, C. / Moore, A. / Hotamisligil, G.S.
History
DepositionJun 12, 2015Deposition site: RCSB / Processing site: PDBE
Revision 1.0Jun 24, 2015Provider: repository / Type: Initial release
Revision 1.1Jan 13, 2016Group: Database references
Revision 1.2Jan 10, 2024Group: 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 / struct_ncs_dom_lim
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession ..._database_2.pdbx_DOI / _database_2.pdbx_database_accession / _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

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Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

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Assembly

Deposited unit
A: Fatty acid-binding protein, adipocyte
H: Fab CA33 Heavy chain
L: Fab CA33 light chain
B: Fatty acid-binding protein, adipocyte
C: Fab CA33 Heavy chain
D: Fab CA33 light chain


Theoretical massNumber of molelcules
Total (without water)124,1396
Polymers124,1396
Non-polymers00
Water0
1
A: Fatty acid-binding protein, adipocyte
H: Fab CA33 Heavy chain
L: Fab CA33 light chain


Theoretical massNumber of molelcules
Total (without water)62,0703
Polymers62,0703
Non-polymers00
Water0
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
2
B: Fatty acid-binding protein, adipocyte
C: Fab CA33 Heavy chain
D: Fab CA33 light chain


Theoretical massNumber of molelcules
Total (without water)62,0703
Polymers62,0703
Non-polymers00
Water0
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
Unit cell
Length a, b, c (Å)65.270, 101.950, 95.320
Angle α, β, γ (deg.)90.00, 90.03, 90.00
Int Tables number4
Space group name H-MP1211
Noncrystallographic symmetry (NCS)NCS domain:
IDEns-IDDetails
11A
21B
12H
22C
13L
23D

NCS domain segments:

Component-ID: 0 / Refine code: 0

Dom-IDEns-IDBeg auth comp-IDBeg label comp-IDEnd auth comp-IDEnd label comp-IDAuth asym-IDLabel asym-IDAuth seq-IDLabel seq-ID
11CYSCYSALAALAAA1 - 1312 - 132
21CYSCYSALAALABD1 - 1312 - 132
12GLNGLNVALVALHB1 - 2181 - 218
22GLNGLNVALVALCE1 - 2181 - 218
13ASPASPARGARGLC1 - 2161 - 216
23ASPASPARGARGDF1 - 2161 - 216

NCS ensembles :
ID
1
2
3

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Components

#1: Protein Fatty acid-binding protein, adipocyte / AP2 / 3T3-L1 lipid-binding protein / Adipocyte lipid-binding protein / ALBP / Adipocyte-type fatty ...AP2 / 3T3-L1 lipid-binding protein / Adipocyte lipid-binding protein / ALBP / Adipocyte-type fatty acid-binding protein / AFABP / Fatty acid-binding protein 4 / Myelin P2 protein homolog / P15 / P2 adipocyte protein / Protein 422


Mass: 14670.884 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Mus musculus (house mouse) / Gene: Fabp4, Ap2 / Production host: Escherichia coli BL21(DE3) (bacteria) / References: UniProt: P04117
#2: Antibody Fab CA33 Heavy chain


Mass: 23379.191 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Oryctolagus cuniculus (rabbit) / Production host: Cricetulus griseus (Chinese hamster)
#3: Antibody Fab CA33 light chain


Mass: 24019.506 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Oryctolagus cuniculus (rabbit) / Production host: Cricetulus griseus (Chinese hamster)

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Experimental details

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Experiment

ExperimentMethod: X-RAY DIFFRACTION

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Sample preparation

CrystalDensity Matthews: 2.55 Å3/Da / Density % sol: 51.85 %
Crystal growTemperature: 296 K / Method: vapor diffusion, sitting drop
Details: 0.1M Hepes pH 7.5, 0.2M NH2SO4, 16% PEG 4K and 10% isopropanol

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Data collection

DiffractionMean temperature: 77 K
Diffraction sourceSource: SYNCHROTRON / Site: Diamond / Beamline: I02 / Wavelength: 0.97949 Å
DetectorType: DECTRIS PILATUS 6M-F / Detector: PIXEL / Date: May 29, 2013
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.97949 Å / Relative weight: 1
ReflectionResolution: 2.95→54.97 Å / Num. obs: 26312 / % possible obs: 99.2 % / Redundancy: 6.16 % / Rmerge(I) obs: 0.18 / Net I/σ(I): 8.3
Reflection shellResolution: 2.95→3.09 Å / Num. unique all: 3489

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Processing

Software
NameVersionClassification
REFMAC5.8.0049refinement
xia2data reduction
SCALAdata scaling
PHASERphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 1LIE

1lie


Resolution: 3→54.97 Å / Cor.coef. Fo:Fc: 0.938 / Cor.coef. Fo:Fc free: 0.884 / SU B: 21.712 / SU ML: 0.386 / Cross valid method: THROUGHOUT / ESU R Free: 0.509 / Stereochemistry target values: MAXIMUM LIKELIHOOD / Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS
RfactorNum. reflection% reflectionSelection details
Rfree0.26464 2466 9.9 %RANDOM
Rwork0.18636 ---
obs0.19425 22426 98.87 %-
Solvent computationIon probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å / Solvent model: MASK
Displacement parametersBiso mean: 60.654 Å2
Baniso -1Baniso -2Baniso -3
1--0.25 Å2-0 Å2-5.01 Å2
2---3.51 Å2-0 Å2
3---3.77 Å2
Refinement stepCycle: 1 / Resolution: 3→54.97 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms8541 0 0 0 8541
Refine LS restraints
Refine-IDTypeDev idealDev ideal targetNumber
X-RAY DIFFRACTIONr_bond_refined_d0.0130.028740
X-RAY DIFFRACTIONr_bond_other_d0.0040.028054
X-RAY DIFFRACTIONr_angle_refined_deg1.6221.95411901
X-RAY DIFFRACTIONr_angle_other_deg1.085318667
X-RAY DIFFRACTIONr_dihedral_angle_1_deg7.3151116
X-RAY DIFFRACTIONr_dihedral_angle_2_deg37.52524.118323
X-RAY DIFFRACTIONr_dihedral_angle_3_deg20.143151415
X-RAY DIFFRACTIONr_dihedral_angle_4_deg19.1351536
X-RAY DIFFRACTIONr_chiral_restr0.0850.21373
X-RAY DIFFRACTIONr_gen_planes_refined0.0080.0219789
X-RAY DIFFRACTIONr_gen_planes_other0.0040.021883
X-RAY DIFFRACTIONr_nbd_refined
X-RAY DIFFRACTIONr_nbd_other
X-RAY DIFFRACTIONr_nbtor_refined
X-RAY DIFFRACTIONr_nbtor_other
X-RAY DIFFRACTIONr_xyhbond_nbd_refined
X-RAY DIFFRACTIONr_xyhbond_nbd_other
X-RAY DIFFRACTIONr_metal_ion_refined
X-RAY DIFFRACTIONr_metal_ion_other
X-RAY DIFFRACTIONr_symmetry_vdw_refined
X-RAY DIFFRACTIONr_symmetry_vdw_other
X-RAY DIFFRACTIONr_symmetry_hbond_refined
X-RAY DIFFRACTIONr_symmetry_hbond_other
X-RAY DIFFRACTIONr_symmetry_metal_ion_refined
X-RAY DIFFRACTIONr_symmetry_metal_ion_other
X-RAY DIFFRACTIONr_mcbond_it4.8435.9764488
X-RAY DIFFRACTIONr_mcbond_other4.8425.9774487
X-RAY DIFFRACTIONr_mcangle_it7.6448.9565596
X-RAY DIFFRACTIONr_mcangle_other7.6438.9565597
X-RAY DIFFRACTIONr_scbond_it4.6636.2684252
X-RAY DIFFRACTIONr_scbond_other4.6636.2694253
X-RAY DIFFRACTIONr_scangle_it
X-RAY DIFFRACTIONr_scangle_other7.339.2256306
X-RAY DIFFRACTIONr_long_range_B_refined10.83247.1689257
X-RAY DIFFRACTIONr_long_range_B_other10.83247.1719258
X-RAY DIFFRACTIONr_rigid_bond_restr
X-RAY DIFFRACTIONr_sphericity_free
X-RAY DIFFRACTIONr_sphericity_bonded
Refine LS restraints NCS

Refine-ID: X-RAY DIFFRACTION / Type: interatomic distance / Weight position: 0.05

Ens-IDDom-IDAuth asym-IDNumberRms dev position (Å)
11A72800.12
12B72800.12
21H107110.12
22C107110.12
31L107540.14
32D107540.14
LS refinement shellResolution: 3→3.078 Å / Total num. of bins used: 20
RfactorNum. reflection% reflection
Rfree0.335 189 -
Rwork0.282 1679 -
obs--98.16 %

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