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- PDB-6m6f: Solution structure of disulfide bond mutaion of the core domain o... -

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Basic information

Entry
Database: PDB / ID: 6m6f
TitleSolution structure of disulfide bond mutaion of the core domain of Fibroblast growth factor 21 (FGF21)
ComponentsFibroblast growth factor 21
KeywordsHORMONE / Disulfide bond mutaion / beta-trefoil conformation / beta-klotho binding / Metabolic regulator
Function / homology
Function and homology information


positive regulation of triglyceride catabolic process / Cellular hexose transport / response to methionine / Assembly of active LPL and LIPC lipase complexes / positive regulation of MAPKKK cascade by fibroblast growth factor receptor signaling pathway / regulation of low-density lipoprotein particle clearance / fibroblast growth factor receptor binding / endothelial cell apoptotic process / positive regulation of low-density lipoprotein receptor activity / cellular response to glucagon stimulus ...positive regulation of triglyceride catabolic process / Cellular hexose transport / response to methionine / Assembly of active LPL and LIPC lipase complexes / positive regulation of MAPKKK cascade by fibroblast growth factor receptor signaling pathway / regulation of low-density lipoprotein particle clearance / fibroblast growth factor receptor binding / endothelial cell apoptotic process / positive regulation of low-density lipoprotein receptor activity / cellular response to glucagon stimulus / cellular response to low-density lipoprotein particle stimulus / fibroblast growth factor receptor signaling pathway / negative regulation of endothelial cell apoptotic process / endoplasmic reticulum unfolded protein response / regulation of cell migration / response to nutrient levels / response to activity / cellular response to glucose stimulus / positive regulation of glucose import / animal organ morphogenesis / growth factor activity / cellular response to xenobiotic stimulus / cell-cell signaling / positive regulation of cold-induced thermogenesis / cell differentiation / positive regulation of ERK1 and ERK2 cascade / positive regulation of protein phosphorylation / positive regulation of cell population proliferation / positive regulation of gene expression / signal transduction / extracellular space / extracellular region / cytoplasm
Similarity search - Function
Fibroblast growth factor 15/19/21 / HBGF/FGF family signature. / Fibroblast growth factor family / Fibroblast growth factor / Acidic and basic fibroblast growth factor family. / Cytokine IL1/FGF
Similarity search - Domain/homology
Fibroblast growth factor 21
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodSOLUTION NMR / simulated annealing
AuthorsZhu, L. / Zhao, H. / Wang, J.
Funding support China, 2items
OrganizationGrant numberCountry
National Natural Science Foundation of China (NSFC)U1532269 China
National Natural Science Foundation of China (NSFC)31100539 China
CitationJournal: Embo Rep. / Year: 2021
Title: Dynamic folding modulation generates FGF21 variant against diabetes.
Authors: Zhu, L. / Zhao, H. / Liu, J. / Cai, H. / Wu, B. / Liu, Z. / Zhou, S. / Liu, Q. / Li, X. / Bao, B. / Liu, J. / Dai, H. / Wang, J.
History
DepositionMar 14, 2020Deposition site: PDBJ / Processing site: PDBJ
Revision 1.0Jan 20, 2021Provider: repository / Type: Initial release
Revision 1.1Mar 3, 2021Group: Database references / Category: citation / Item: _citation.journal_volume / _citation.year
Revision 1.2Jun 14, 2023Group: Database references / Other / Category: database_2 / pdbx_database_status
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession / _pdbx_database_status.status_code_nmr_data

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Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

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Assembly

Deposited unit
A: Fibroblast growth factor 21


Theoretical massNumber of molelcules
Total (without water)14,1041
Polymers14,1041
Non-polymers00
Water0
1


  • Idetical with deposited unit
  • defined by author
  • Evidence: gel filtration
TypeNameSymmetry operationNumber
identity operation1_5551
Buried area0 Å2
ΔGint0 kcal/mol
Surface area7970 Å2
NMR ensembles
DataCriteria
Number of conformers (submitted / calculated)10 / 200structures with the lowest energy
RepresentativeModel #1closest to the average

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Components

#1: Protein Fibroblast growth factor 21 / / FGF-21


Mass: 14103.977 Da / Num. of mol.: 1
Mutation: D23S, D24G, A25P, Q26H, Q28L, T29S, E30S, A31C, G43C
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: FGF21 / Production host: Escherichia coli K-12 (bacteria) / Strain (production host): K-12 / References: UniProt: Q9NSA1

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Experimental details

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Experiment

ExperimentMethod: SOLUTION NMR
NMR experiment
Conditions-IDExperiment-IDSolution-IDSample stateSpectrometer-IDType
111isotropic12D 1H-15N HSQC
122isotropic12D 1H-15N HSQC
133isotropic12D 1H-15N HSQC
142isotropic23D CBCA(CO)NH
152isotropic23D HNCO
162isotropic23D HNCA
172isotropic23D HN(CA)CB
182isotropic23D HBHA(CO)NH
192isotropic23D HN(CO)CA
1102isotropic23D HN(CA)CO
1112isotropic23D 1H-13C NOESY
1121isotropic13D 1H-15N NOESY
1133isotropic13D (H)CCH-TOCSY
1143isotropic13D (H)CCH-COSY
1153isotropic23D 1H-13C NOESY

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Sample preparation

Details
TypeSolution-IDContentsLabelSolvent system
solution10.5 mM [U-99% 15N] FGF21SS, 20 mM sodium phosphate, 100 mM sodium chloride, 0.2 % w/v sodium azide, 90% H2O/10% D2O15N_sample90% H2O/10% D2O
solution20.5 mM [U-99% 13C; U-99% 15N] FGF21SS, 20 mM sodium phosphate, 100 mM sodium chloride, 0.2 % w/v sodium azide, 90% H2O/10% D2O13C_15N_sample90% H2O/10% D2O
solution30.5 mM [U-99% 13C; U-99% 15N] FGF21SS, 20 mM sodium phosphate, 100 mM sodium chloride, 0.2 % w/v sodium azide, 100% D2O13C_15N_sample in D2O100% D2O
Sample
Conc. (mg/ml)ComponentIsotopic labelingSolution-ID
0.5 mMFGF21SS[U-99% 15N]1
20 mMsodium phosphatenatural abundance1
100 mMsodium chloridenatural abundance1
0.2 % w/vsodium azidenatural abundance1
0.5 mMFGF21SS[U-99% 13C; U-99% 15N]2
20 mMsodium phosphatenatural abundance2
100 mMsodium chloridenatural abundance2
0.2 % w/vsodium azidenatural abundance2
0.5 mMFGF21SS[U-99% 13C; U-99% 15N]3
20 mMsodium phosphatenatural abundance3
100 mMsodium chloridenatural abundance3
0.2 % w/vsodium azidenatural abundance3
Sample conditionsIonic strength: 160 mM / Label: condition_1 / pH: 7.0 / Pressure: 1 atm / Temperature: 298 K

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NMR measurement

NMR spectrometer
TypeManufacturerModelField strength (MHz)Spectrometer-ID
Bruker AVANCE IIIBrukerAVANCE III6001
Bruker AVANCE IIIBrukerAVANCE III8502

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Processing

NMR software
NameDeveloperClassification
TopSpinBruker Biospincollection
NMRPipeDelaglio, Grzesiek, Vuister, Zhu, Pfeifer and Baxprocessing
CcpNmr AnalysisCCPNchemical shift assignment
X-PLOR NIHSchwieters, Kuszewski, Tjandra and Clorestructure calculation
X-PLOR NIHSchwieters, Kuszewski, Tjandra and Clorerefinement
RefinementMethod: simulated annealing / Software ordinal: 5
NMR representativeSelection criteria: closest to the average
NMR ensembleConformer selection criteria: structures with the lowest energy
Conformers calculated total number: 200 / Conformers submitted total number: 10

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