4L3O | pdb_00004l3o

Crystal Structure of SIRT2 in complex with the macrocyclic peptide S2iL5

External Resource: Annotation

Domain Annotation: SCOP2 Classification
Domain Annotation: ECOD Classification
Domain Annotation: CATH
Protein Family Annotation
Gene Ontology: Gene Product Annotation
InterPro: Protein Family Classification
Pharos: Disease Associations
Protein Modification Annotation

Domain Annotation: SCOP2 Classification SCOP2 Database Homepage

Chains	Type	Family Name	Domain Identifier	Family Identifier	Provenance Source (Version)
D	SCOP2B Superfamily	DHS-like NAD/FAD-binding domain	8034236	3001728	SCOP2B (2022-06-29)
C	SCOP2B Superfamily	DHS-like NAD/FAD-binding domain	8034236	3001728	SCOP2B (2022-06-29)
B	SCOP2B Superfamily	DHS-like NAD/FAD-binding domain	8034236	3001728	SCOP2B (2022-06-29)
A	SCOP2B Superfamily	DHS-like NAD/FAD-binding domain	8034236	3001728	SCOP2B (2022-06-29)

Domain Annotation: ECOD Classification ECOD Database Homepage

Chains	Family Name	Domain Identifier	Architecture	Possible Homology	Homology	Topology	Family	Provenance Source (Version)
D	SIR2_1st	e4l3oD1	A: a/b three-layered sandwiches	X: Rossmann-like	H: Rossmann-related	T: DHS-like NAD/FAD-binding domain	F: SIR2_1st	ECOD (1.6)
D	SIR2_2nd	e4l3oD2	A: few secondary structure elements	X: Rubredoxin-like	H: Rubredoxin-related	T: Rubredoxin-related	F: SIR2_2nd	ECOD (1.6)
C	SIR2_1st	e4l3oC1	A: a/b three-layered sandwiches	X: Rossmann-like	H: Rossmann-related	T: DHS-like NAD/FAD-binding domain	F: SIR2_1st	ECOD (1.6)
C	SIR2_2nd	e4l3oC2	A: few secondary structure elements	X: Rubredoxin-like	H: Rubredoxin-related	T: Rubredoxin-related	F: SIR2_2nd	ECOD (1.6)
B	SIR2_1st	e4l3oB1	A: a/b three-layered sandwiches	X: Rossmann-like	H: Rossmann-related	T: DHS-like NAD/FAD-binding domain	F: SIR2_1st	ECOD (1.6)
B	SIR2_2nd	e4l3oB2	A: few secondary structure elements	X: Rubredoxin-like	H: Rubredoxin-related	T: Rubredoxin-related	F: SIR2_2nd	ECOD (1.6)
A	SIR2_1st	e4l3oA1	A: a/b three-layered sandwiches	X: Rossmann-like	H: Rossmann-related	T: DHS-like NAD/FAD-binding domain	F: SIR2_1st	ECOD (1.6)
A	SIR2_2nd	e4l3oA2	A: few secondary structure elements	X: Rubredoxin-like	H: Rubredoxin-related	T: Rubredoxin-related	F: SIR2_2nd	ECOD (1.6)

Domain Annotation: CATH CATH Database Homepage

Chain	Domain	Class	Architecture	Topology	Homology	Provenance Source (Version)
D	3.40.50.1220	Alpha Beta	3-Layer(aba) Sandwich	Rossmann fold	TPP-binding domain	CATH (4.3.0)
D	3.30.1600.10	Alpha Beta	2-Layer Sandwich	SIR2/SIRT2 'Small Domain'	SIR2/SIRT2 'Small Domain'	CATH (4.3.0)
C	3.40.50.1220	Alpha Beta	3-Layer(aba) Sandwich	Rossmann fold	TPP-binding domain	CATH (4.3.0)
C	3.30.1600.10	Alpha Beta	2-Layer Sandwich	SIR2/SIRT2 'Small Domain'	SIR2/SIRT2 'Small Domain'	CATH (4.3.0)
B	3.40.50.1220	Alpha Beta	3-Layer(aba) Sandwich	Rossmann fold	TPP-binding domain	CATH (4.3.0)
B	3.30.1600.10	Alpha Beta	2-Layer Sandwich	SIR2/SIRT2 'Small Domain'	SIR2/SIRT2 'Small Domain'	CATH (4.3.0)
A	3.40.50.1220	Alpha Beta	3-Layer(aba) Sandwich	Rossmann fold	TPP-binding domain	CATH (4.3.0)
A	3.30.1600.10	Alpha Beta	2-Layer Sandwich	SIR2/SIRT2 'Small Domain'	SIR2/SIRT2 'Small Domain'	CATH (4.3.0)

Protein Family Annotation Pfam Database Homepage

Chains	Accession	Name	Description	Comments	Source
A, B, C, D	PF02146	Sir2 family (SIR2)	Sir2 family	-	Family

Gene Ontology: Gene Product Annotation Gene Ontology Database Homepage

Chains	Polymer	Molecular Function	Biological Process	Cellular Component
E, F, G, H	cyclic peptide S2iL5	-	-	-
A, B, C, D	NAD-dependent protein deacetylase sirtuin-2	histone deacetylase binding protein binding binding enzyme binding deacetylase activity protein lysine deacetylase activity catalytic activity, acting on a protein deacylase activity catalytic activity NAD+ binding NAD binding nucleotide binding nucleoside phosphate binding ion binding histone deacetylase binding protein binding binding enzyme binding deacetylase activity protein lysine deacetylase activity catalytic activity, acting on a protein deacylase activity catalytic activity NAD+ binding NAD binding nucleotide binding nucleoside phosphate binding ion binding purine nucleotide binding anion binding adenyl nucleotide binding heterocyclic compound binding small molecule binding NAD-dependent protein demyristoylase activity acyltransferase activity acyltransferase activity, transferring groups other than amino-acyl groups transferase activity pentosyltransferase activity NAD+ poly-ADP-ribosyltransferase activity glycosyltransferase activity tubulin deacetylase activity hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds, in linear amides hydrolase activity hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds histone deacetylase activity histone modifying activity chromatin binding ubiquitin binding ubiquitin-like protein binding histone deacetylase activity, NAD-dependent NAD-dependent protein lysine deacylase activity NAD-dependent protein lysine deacetylase activity histone acetyltransferase binding transcription factor binding DNA-binding transcription factor binding cation binding transition metal ion binding zinc ion binding metal ion binding NAD-dependent protein depalmitoylase activity histone H4K16 deacetylase activity, NAD-dependent histone H4K deacetylase activity	regulation of molecular function positive regulation of molecular function regulation of DNA binding regulation of binding biological regulation positive regulation of binding positive regulation of DNA binding regulation of biological process regulation of cellular process phosphorylation phosphate-containing compound metabolic process regulation of phosphorylation regulation of phosphorus metabolic process cellular process regulation of molecular function positive regulation of molecular function regulation of DNA binding regulation of binding biological regulation positive regulation of binding positive regulation of DNA binding regulation of biological process regulation of cellular process phosphorylation phosphate-containing compound metabolic process regulation of phosphorylation regulation of phosphorus metabolic process cellular process metabolic process phosphorus metabolic process regulation of metabolic process multicellular organismal process oligodendrocyte progenitor proliferation negative regulation of neural precursor cell proliferation cellular developmental process regulation of developmental process negative regulation of biological process cell development regulation of neurogenesis regulation of cell differentiation regulation of gliogenesis regulation of cell development regulation of nervous system development neurogenesis multicellular organism development negative regulation of neurogenesis gliogenesis cell differentiation anatomical structure development negative regulation of cellular process regulation of multicellular organismal process negative regulation of nervous system development negative regulation of cell differentiation negative regulation of oligodendrocyte progenitor proliferation system development regulation of neural precursor cell proliferation developmental process regulation of multicellular organismal development negative regulation of cell population proliferation cell population proliferation negative regulation of developmental process nervous system development negative regulation of gliogenesis negative regulation of cell development regulation of cell population proliferation neural precursor cell proliferation negative regulation of multicellular organismal process regulation of oligodendrocyte progenitor proliferation skeletal muscle cell differentiation skeletal muscle tissue development striated muscle tissue development muscle structure development skeletal muscle organ development regulation of skeletal muscle cell differentiation negative regulation of skeletal muscle cell differentiation muscle tissue development muscle organ development animal organ development tissue development negative regulation of satellite cell differentiation skeletal muscle satellite cell differentiation peptidyl-lysine deacetylation peptidyl-lysine modification primary metabolic process macromolecule deacylation protein deacetylation protein deacylation macromolecule modification peptidyl-amino acid modification protein metabolic process macromolecule metabolic process protein modification process regulation of cell cycle phase transition cell cycle phase transition exit from mitosis mitotic cell cycle cellular component organization regulation of mitotic cell cycle cell cycle cellular component organization or biogenesis regulation of cell cycle cell cycle process mitotic nuclear division regulation of cell cycle process organelle fission regulation of mitotic cell cycle phase transition nuclear division organelle organization mitotic cell cycle process regulation of exit from mitosis mitotic cell cycle phase transition cell division peripheral nervous system axon ensheathment peripheral nervous system development glial cell development myelination Schwann cell development axon ensheathment ensheathment of neurons glial cell differentiation myelination in peripheral nervous system Schwann cell differentiation cellular response to stimulus positive regulation of response to biotic stimulus pattern recognition receptor signaling pathway response to stimulus regulation of NLRP3 inflammasome complex assembly regulation of signal transduction response to biotic stimulus intracellular signal transduction cell communication cellular component biogenesis immune response-activating signaling pathway cellular component assembly inflammasome-mediated signaling pathway positive regulation of immune response canonical inflammasome complex assembly regulation of immune system process signal transduction negative regulation of NLRP3 inflammasome complex assembly positive regulation of immune system process innate immune response-activating signaling pathway negative regulation of cellular component organization immune response response to other organism regulation of innate immune response response to external stimulus regulation of inflammasome-mediated signaling pathway negative regulation of protein-containing complex assembly regulation of response to stimulus defense response to other organism regulation of pattern recognition receptor signaling pathway NLRP3 inflammasome complex assembly positive regulation of defense response activation of innate immune response regulation of immune response inflammatory response activation of immune response cytoplasmic pattern recognition receptor signaling pathway regulation of defense response regulation of response to biotic stimulus biological process involved in interspecies interaction between organisms regulation of cellular component organization regulation of response to external stimulus intracellular receptor signaling pathway signaling negative regulation of signaling negative regulation of cytoplasmic pattern recognition receptor signaling pathway negative regulation of intracellular signal transduction positive regulation of biological process regulation of cytoplasmic pattern recognition receptor signaling pathway negative regulation of cell communication positive regulation of response to stimulus regulation of protein-containing complex assembly positive regulation of response to external stimulus immune response-regulating signaling pathway regulation of intracellular signal transduction regulation of response to stress response to stress innate immune response protein-containing complex assembly response to external biotic stimulus regulation of signaling positive regulation of innate immune response defense response negative regulation of response to stimulus protein-containing complex organization defense response to symbiont regulation of cellular component biogenesis negative regulation of signal transduction negative regulation of immune system process immune system process regulation of cell communication negative regulation of inflammasome-mediated signaling pathway response to decreased oxygen levels cellular response to oxygen levels cellular response to hypoxia cellular response to decreased oxygen levels cellular response to chemical stimulus cellular response to stress response to hypoxia response to chemical response to oxygen levels response to abiotic stimulus response to redox state catabolic process autophagy process utilizing autophagic mechanism regulation of biosynthetic process epigenetic regulation of gene expression regulation of macromolecule metabolic process gene expression macromolecule biosynthetic process regulation of gene expression biosynthetic process chromatin organization chromatin remodeling regulation of macromolecule biosynthetic process oxoacid metabolic process ketone metabolic process regulation of lipid metabolic process lipid biosynthetic process organic acid biosynthetic process organic acid metabolic process carboxylic acid biosynthetic process regulation of primary metabolic process positive regulation of fatty acid biosynthetic process positive regulation of metabolic process regulation of small molecule metabolic process positive regulation of biosynthetic process positive regulation of lipid metabolic process small molecule metabolic process positive regulation of cellular process positive regulation of fatty acid metabolic process fatty acid metabolic process monocarboxylic acid biosynthetic process small molecule biosynthetic process carboxylic acid metabolic process fatty acid biosynthetic process regulation of ketone metabolic process positive regulation of lipid biosynthetic process regulation of fatty acid metabolic process regulation of fatty acid biosynthetic process monocarboxylic acid metabolic process regulation of lipid biosynthetic process positive regulation of small molecule metabolic process lipid metabolic process positive regulation of proteasomal protein catabolic process positive regulation of protein metabolic process proteolysis involved in protein catabolic process proteasome-mediated ubiquitin-dependent protein catabolic process macromolecule catabolic process regulation of ubiquitin-dependent protein catabolic process positive regulation of ubiquitin-dependent protein catabolic process regulation of proteolysis regulation of proteolysis involved in protein catabolic process modification-dependent macromolecule catabolic process proteolysis positive regulation of macromolecule metabolic process regulation of protein metabolic process proteasomal protein catabolic process protein catabolic process regulation of catabolic process positive regulation of protein catabolic process positive regulation of proteolysis involved in protein catabolic process positive regulation of catabolic process regulation of proteasomal ubiquitin-dependent protein catabolic process modification-dependent protein catabolic process positive regulation of proteolysis regulation of proteasomal protein catabolic process positive regulation of proteasomal ubiquitin-dependent protein catabolic process ubiquitin-dependent protein catabolic process regulation of protein catabolic process positive regulation of cell division regulation of cell division positive regulation of programmed cell death regulation of apoptotic process regulation of programmed cell death cell death positive regulation of apoptotic process regulation of execution phase of apoptosis positive regulation of execution phase of apoptosis execution phase of apoptosis apoptotic process programmed cell death response to oxidative stress cellular response to oxidative stress cellular response to chemical stress negative regulation of metabolic process reactive oxygen species metabolic process negative regulation of reactive oxygen species metabolic process regulation of reactive oxygen species metabolic process subtelomeric heterochromatin formation negative regulation of macromolecule metabolic process heterochromatin formation heterochromatin organization negative regulation of gene expression constitutive heterochromatin formation negative regulation of biosynthetic process negative regulation of macromolecule biosynthetic process negative regulation of gene expression, epigenetic response to nutrient levels cellular response to caloric restriction response to caloric restriction negative regulation of catabolic process regulation of autophagy negative regulation of autophagy negative regulation of protein catabolic process negative regulation of protein metabolic process RNA metabolic process negative regulation of RNA biosynthetic process RNA biosynthetic process nucleobase-containing compound metabolic process DNA-templated transcription nucleic acid biosynthetic process regulation of RNA metabolic process transcription by RNA polymerase II negative regulation of nucleobase-containing compound metabolic process regulation of nucleobase-containing compound metabolic process regulation of RNA biosynthetic process regulation of transcription by RNA polymerase II negative regulation of DNA-templated transcription negative regulation of transcription by RNA polymerase II nucleobase-containing compound biosynthetic process nucleic acid metabolic process regulation of DNA-templated transcription negative regulation of RNA metabolic process positive regulation of DNA-templated transcription positive regulation of macromolecule biosynthetic process positive regulation of transcription by RNA polymerase II positive regulation of RNA metabolic process positive regulation of RNA biosynthetic process fat cell differentiation negative regulation of fat cell differentiation regulation of fat cell differentiation regulation of myelination regulation of protein modification process regulation of protein phosphorylation regulation of peptidyl-threonine phosphorylation negative regulation of phosphate metabolic process negative regulation of protein modification process peptidyl-threonine modification protein phosphorylation negative regulation of protein phosphorylation negative regulation of peptidyl-threonine phosphorylation negative regulation of phosphorus metabolic process negative regulation of phosphorylation peptidyl-threonine phosphorylation tubulin deacetylation mitotic nuclear membrane reassembly membrane biogenesis nuclear membrane reassembly endomembrane system organization membrane organization nuclear membrane organization membrane assembly nucleus organization mitotic nuclear membrane organization nuclear envelope organization response to epinephrine cellular response to epinephrine stimulus lipid catabolic process head development brain development substantia nigra development central nervous system development midbrain development neural nucleus development regulation of muscle tissue development regulation of striated muscle tissue development negative regulation of muscle tissue development negative regulation of muscle organ development regulation of muscle organ development negative regulation of striated muscle tissue development positive regulation of oocyte maturation sexual reproduction regulation of reproductive process reproductive process regulation of oocyte maturation cellular process involved in reproduction in multicellular organism positive regulation of cell maturation developmental process involved in reproduction female gamete generation gamete generation oocyte development positive regulation of developmental process positive regulation of cell differentiation cell maturation regulation of cell maturation positive regulation of reproductive process multicellular organismal reproductive process oogenesis positive regulation of cell development developmental maturation anatomical structure maturation germ cell development oocyte maturation oocyte differentiation meiotic cell cycle positive regulation of organelle organization positive regulation of cellular component organization meiotic cell cycle process positive regulation of cell cycle process meiotic nuclear division regulation of meiotic cell cycle positive regulation of nuclear division positive regulation of meiotic cell cycle regulation of organelle organization positive regulation of cell cycle regulation of meiotic nuclear division regulation of nuclear division positive regulation of meiotic nuclear division nucleolar chromatin organization rDNA heterochromatin formation nucleolus organization facultative heterochromatin formation regulation of chromosome segregation metaphase chromosome alignment localization chromosome localization organelle localization regulation of attachment of spindle microtubules to kinetochore chromosome segregation positive regulation of chromosome segregation attachment of spindle microtubules to kinetochore positive regulation of attachment of spindle microtubules to kinetochore nuclear chromosome segregation	axon cell projection cellular anatomical structure main axon juxtaparanode region of axon neuron projection plasma membrane bounded cell projection somatodendritic compartment cell body perikaryon neuronal cell body cell-cell junction anchoring junction cell junction axon cell projection cellular anatomical structure main axon juxtaparanode region of axon neuron projection plasma membrane bounded cell projection somatodendritic compartment cell body perikaryon neuronal cell body cell-cell junction anchoring junction cell junction paranodal junction intracellular anatomical structure cytoplasm cytosol intracellular organelle organelle membraneless organelle intracellular membraneless organelle chromosome chromatin heterochromatin perinuclear region of cytoplasm cytoskeleton spindle microtubule cytoskeleton chromosome, telomeric region chromosomal region polymeric cytoskeletal fiber supramolecular fiber microtubule supramolecular polymer supramolecular complex membrane-bounded organelle mitochondrion intracellular membrane-bounded organelle midbody nucleus membrane-enclosed lumen nucleolus intracellular organelle lumen organelle lumen nuclear lumen myelin sheath paranode region of axon centrosome microtubule organizing center centriole cell periphery plasma membrane membrane glial cell projection mitotic spindle growth cone distal axon site of polarized growth protein-containing complex chromatin silencing complex nuclear protein-containing complex compact myelin Schmidt-Lanterman incisure lateral loop meiotic spindle

InterPro: Protein Family Classification InterPro Database Homepage

Chains	Accession	Name	Type
A, B, C, D	IPR003000	Sirtuin family	Family
A, B, C, D	IPR029035	DHS-like NAD/FAD-binding domain superfamily	Homologous Superfamily
A, B, C, D	IPR017328	Sirtuin, class I	Family
A, B, C, D	IPR026590	Sirtuin family, catalytic core domain	Domain
A, B, C, D	IPR050134	NAD-dependent sirtuin protein deacylases	Family
A, B, C, D	IPR026591	Sirtuin, catalytic core small domain superfamily	Homologous Superfamily

Pharos: Disease Associations Pharos Homepage Annotation

Chains	Drug Target	Associated Disease
A, B, C, D	Pharos: Q8IXJ6	neurodegenerative disease adrenal cortex carcinoma large cell medulloblastoma Disturbance in mood medulloblastoma osteosarcoma

Protein Modification Annotation

Modified Residue(s)
Chain	Residue(s)	Description
E, F, G, H	ACY	RESID: AA0441 PSI-MOD : (2-aminosuccinimidyl)acetic acid (Asp) MOD:00952 , (2-aminosuccinimidyl)acetic acid (Asn) MOD:01624
E, F, G, H	FAK	Parent Component: LYS RESID: AA0441
E, F, G, H	NH2	RESID: AA0441 , AA0081 , AA0083 , AA0084 , AA0086 , AA0087 , AA0088 , AA0090 , AA0091 , AA0092 , AA0093 , AA0095 , AA0096 , AA0097 , AA0098 , AA0099 , AA0100 PSI-MOD : (2-aminosuccinimidyl)acetic acid (Asp) MOD:00952 , (2-aminosuccinimidyl)acetic acid (Asn) MOD:01624 , L-alanine amide MOD:00090 , L-asparagine amide MOD:00092 , L-aspartic acid 1-amide MOD:00093 , L-glutamine amide MOD:00095 , L-glutamic acid 1-amide MOD:00096 , glycine amide MOD:00097 , L-isoleucine amide MOD:00099 , L-leucine amide MOD:00100 , L-lysine amide MOD:00101 , L-methionine amide MOD:00102 , L-proline amide MOD:00104 , L-serine amide MOD:00105 , L-threonine amide MOD:00106 , L-tryptophan amide MOD:00107 , L-tyrosine amide MOD:00108 , L-valine amide MOD:00109

RCSB PDB Core Operations are funded by the U.S. National Science Foundation (DBI-2321666), the US Department of Energy (DE-SC0019749), and the National Cancer Institute, National Institute of Allergy and Infectious Diseases, and National Institute of General Medical Sciences of the National Institutes of Health under grant R01GM157729.