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- PDB-1hiq: PARADOXICAL STRUCTURE AND FUNCTION IN A MUTANT HUMAN INSULIN ASSO... -

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Entry
Database: PDB / ID: 1hiq
TitlePARADOXICAL STRUCTURE AND FUNCTION IN A MUTANT HUMAN INSULIN ASSOCIATED WITH DIABETES MELLITUS
Components(INSULIN) x 2
KeywordsHORMONE
Function / homology
Function and homology information


negative regulation of glycogen catabolic process / positive regulation of nitric oxide mediated signal transduction / negative regulation of fatty acid metabolic process / negative regulation of feeding behavior / Signaling by Insulin receptor / IRS activation / regulation of protein secretion / Insulin processing / positive regulation of peptide hormone secretion / positive regulation of respiratory burst ...negative regulation of glycogen catabolic process / positive regulation of nitric oxide mediated signal transduction / negative regulation of fatty acid metabolic process / negative regulation of feeding behavior / Signaling by Insulin receptor / IRS activation / regulation of protein secretion / Insulin processing / positive regulation of peptide hormone secretion / positive regulation of respiratory burst / negative regulation of acute inflammatory response / Regulation of gene expression in beta cells / alpha-beta T cell activation / positive regulation of dendritic spine maintenance / Synthesis, secretion, and deacylation of Ghrelin / negative regulation of respiratory burst involved in inflammatory response / activation of protein kinase B activity / negative regulation of protein secretion / negative regulation of gluconeogenesis / positive regulation of insulin receptor signaling pathway / positive regulation of glycogen biosynthetic process / fatty acid homeostasis / Signal attenuation / FOXO-mediated transcription of oxidative stress, metabolic and neuronal genes / negative regulation of lipid catabolic process / positive regulation of lipid biosynthetic process / negative regulation of oxidative stress-induced intrinsic apoptotic signaling pathway / regulation of protein localization to plasma membrane / nitric oxide-cGMP-mediated signaling / transport vesicle / COPI-mediated anterograde transport / positive regulation of nitric-oxide synthase activity / Insulin receptor recycling / negative regulation of reactive oxygen species biosynthetic process / insulin-like growth factor receptor binding / positive regulation of brown fat cell differentiation / NPAS4 regulates expression of target genes / neuron projection maintenance / endoplasmic reticulum-Golgi intermediate compartment membrane / positive regulation of mitotic nuclear division / Insulin receptor signalling cascade / positive regulation of glycolytic process / positive regulation of cytokine production / endosome lumen / positive regulation of long-term synaptic potentiation / acute-phase response / positive regulation of D-glucose import / positive regulation of protein secretion / insulin receptor binding / positive regulation of cell differentiation / Regulation of insulin secretion / wound healing / positive regulation of neuron projection development / hormone activity / negative regulation of protein catabolic process / regulation of synaptic plasticity / positive regulation of protein localization to nucleus / Golgi lumen / vasodilation / cognition / glucose metabolic process / insulin receptor signaling pathway / cell-cell signaling / glucose homeostasis / regulation of protein localization / PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling / positive regulation of cell growth / protease binding / secretory granule lumen / positive regulation of canonical NF-kappaB signal transduction / positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction / positive regulation of MAPK cascade / positive regulation of cell migration / G protein-coupled receptor signaling pathway / endoplasmic reticulum lumen / Amyloid fiber formation / Golgi membrane / negative regulation of gene expression / positive regulation of cell population proliferation / positive regulation of gene expression / regulation of DNA-templated transcription / extracellular space / extracellular region / identical protein binding
Similarity search - Function
Insulin / Insulin family / Insulin-like / Insulin/IGF/Relaxin family / Insulin / insulin-like growth factor / relaxin family. / Insulin, conserved site / Insulin family signature. / Insulin-like superfamily
Similarity search - Domain/homology
Biological speciesHomo sapiens (human)
MethodSOLUTION NMR
AuthorsHua, Q.X. / Shoelson, S.E. / Inouye, K. / Weiss, M.A.
Citation
Journal: Proc.Natl.Acad.Sci.USA / Year: 1993
Title: Paradoxical structure and function in a mutant human insulin associated with diabetes mellitus.
Authors: Hua, Q.X. / Shoelson, S.E. / Inouye, K. / Weiss, M.A.
#1: Journal: Proc.Natl.Acad.Sci.USA / Year: 1992
Title: Structure and Dynamics of Des-Pentapeptide-Insulin in Solution: The Molten-Globule Hypothesis
Authors: Hua, Q.-X. / Kochoyan, M. / Weiss, M.A.
#2: Journal: Nature / Year: 1991
Title: Receptor Binding Redefined by a Structural Switch in a Mutant Human Insulin
Authors: Hua, Q.X. / Shoelson, S.E. / Kochoyan, M. / Weiss, M.A.
History
DepositionMar 5, 1993Processing site: BNL
Revision 1.0Jan 31, 1994Provider: repository / Type: Initial release
Revision 1.1Mar 24, 2008Group: Version format compliance
Revision 1.2Jul 13, 2011Group: Version format compliance
Revision 1.3Nov 29, 2017Group: Derived calculations / Other
Category: pdbx_database_status / struct_conf / struct_conf_type
Item: _pdbx_database_status.process_site
Revision 1.4Nov 13, 2024Group: Data collection / Database references / Structure summary
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / database_2 / pdbx_entry_details / pdbx_modification_feature / struct_ref_seq_dif
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession / _struct_ref_seq_dif.details

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Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

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Assembly

Deposited unit
A: INSULIN
B: INSULIN


Theoretical massNumber of molelcules
Total (without water)5,7582
Polymers5,7582
Non-polymers00
Water00
1


  • Idetical with deposited unit
  • defined by author
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Atom site foot note1: THR B 27 - PRO B 28 MODEL 2 OMEGA =213.93 PEPTIDE BOND DEVIATES SIGNIFICANTLY FROM TRANS CONFORMATION
2: THR B 27 - PRO B 28 MODEL 9 OMEGA =213.50 PEPTIDE BOND DEVIATES SIGNIFICANTLY FROM TRANS CONFORMATION
NMR ensembles
DataCriteria
Number of conformers (submitted / calculated)10 / -
Representative

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Components

#1: Protein/peptide INSULIN


Mass: 2383.698 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / References: UniProt: P01308
#2: Protein/peptide INSULIN


Mass: 3373.857 Da / Num. of mol.: 1 / Mutation: F24S
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Organ: PANCREAS / References: UniProt: P01308
Has protein modificationY

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Experimental details

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Experiment

ExperimentMethod: SOLUTION NMR

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Sample preparation

Crystal grow
*PLUS
Method: other / Details: NMR

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Processing

Software
NameClassification
X-PLORmodel building
X-PLORrefinement
X-PLORphasing
NMR software
NameDeveloperClassification
DGIIHAVELrefinement
X-PLORBRUNGERrefinement
NMR ensembleConformers submitted total number: 10

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