1SZD

Structural basis for nicotinamide cleavage and ADP-ribose transfer by NAD+-dependent Sir2 histone/protein deacetylases

External Resource: Annotation

Domain Annotation: SCOP/SCOPe Classification
Domain Annotation: SCOP2 Classification
Domain Annotation: ECOD Classification
Domain Annotation: CATH
Protein Family Annotation
Gene Ontology: Gene Product Annotation
InterPro: Protein Family Classification
Protein Modification Annotation
Structure Motif: Primary M-CSA Annotation

Domain Annotation: SCOP/SCOPe Classification SCOP-e Database Homepage

Chains	Domain Info	Class	Fold	Superfamily	Family	Domain	Species	Provenance Source (Version)
A	d1szda1	Alpha and beta proteins (a/b)	DHS-like NAD/FAD-binding domain	DHS-like NAD/FAD-binding domain	Sir2 family of transcriptional regulators	Hst2	baker's yeast (Saccharomyces cerevisiae ) [TaxId: 4932 ],	SCOPe (2.08)
A	d1szda2	Artifacts	Tags	Tags	Tags	N-terminal Tags	baker's yeast (Saccharomyces cerevisiae ) [TaxId: 4932 ],	SCOPe (2.08)

Domain Annotation: SCOP2 Classification SCOP2 Database Homepage

Chains	Type	Family Name	Domain Identifier	Family Identifier	Provenance Source (Version)
A	SCOP2B Superfamily	DHS-like NAD/FAD-binding domain	8039531	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)
A	SIR2_1st	e1szdA3	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	KOG2682	e1szdA1	A: few secondary structure elements	X: Rubredoxin-like	H: Rubredoxin-related	T: Rubredoxin-related	F: KOG2682	ECOD (1.6)

Domain Annotation: CATH CATH Database Homepage

Chain	Domain	Class	Architecture	Topology	Homology	Provenance Source (Version)
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	PF02146	Sir2 family (SIR2)	Sir2 family	-	Family
B	PF15511	Centromere kinetochore component CENP-T histone fold (CENP-T_C)	Centromere kinetochore component CENP-T histone fold	CENP-T is a family of vertebral kinetochore proteins that associates directly with CENP-W. The N-terminus of CENP-T proteins interacts directly with the Ndc80 complex in the outer kinetochore. Importantly, the CENP-T-W complex does not directly asso ...	CENP-T is a family of vertebral kinetochore proteins that associates directly with CENP-W. The N-terminus of CENP-T proteins interacts directly with the Ndc80 complex in the outer kinetochore. Importantly, the CENP-T-W complex does not directly associate with CENP-A, but with histone H3 in the centromere region. CENP-T and -W form a hetero-tetramer with CENP-S and -X and bind to a ~100 bp region of nucleosome-free DNA forming a nucleosome-like structure. The DNA-CENP-T-W-S-X complex is likely to be associated with histone H3-containing nucleosomes rather than with CENP-nucleosomes. This domain is the C-terminal histone fold domain of CENP-T, which associates with chromatin [2-3].	Domain

Gene Ontology: Gene Product Annotation Gene Ontology Database Homepage

Chains	Polymer	Molecular Function	Biological Process	Cellular Component
A	NAD-dependent deacetylase HST2	NAD+ binding NAD binding binding nucleotide binding nucleoside phosphate binding ion binding purine nucleotide binding organic cyclic compound binding anion binding adenyl nucleotide binding heterocyclic compound binding small molecule binding cation binding metal ion binding NAD+ binding NAD binding binding nucleotide binding nucleoside phosphate binding ion binding purine nucleotide binding organic cyclic compound binding anion binding adenyl nucleotide binding heterocyclic compound binding small molecule binding cation binding metal ion binding deacetylase activity NAD-dependent histone deacetylase activity protein lysine deacetylase activity catalytic activity, acting on a protein 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 H4K deacetylase activity histone H4K16 deacetylase activity histone modifying activity NAD-dependent protein lysine deacetylase activity catalytic activity NAD-dependent histone H4K16 deacetylase activity transferase activity	regulation of DNA recombination negative regulation of biological process regulation of mitotic recombination regulation of primary metabolic process nucleobase-containing compound metabolic process organic substance metabolic process negative regulation of nucleobase-containing compound metabolic process regulation of nucleobase-containing compound metabolic process negative regulation of macromolecule metabolic process negative regulation of mitotic recombination regulation of biological process DNA recombination negative regulation of metabolic process biological regulation regulation of DNA recombination negative regulation of biological process regulation of mitotic recombination regulation of primary metabolic process nucleobase-containing compound metabolic process organic substance metabolic process negative regulation of nucleobase-containing compound metabolic process regulation of nucleobase-containing compound metabolic process negative regulation of macromolecule metabolic process negative regulation of mitotic recombination regulation of biological process DNA recombination negative regulation of metabolic process biological regulation mitotic recombination primary metabolic process DNA metabolic process regulation of macromolecule metabolic process nucleic acid metabolic process negative regulation of DNA recombination organic cyclic compound metabolic process metabolic process negative regulation of DNA metabolic process macromolecule metabolic process regulation of metabolic process regulation of DNA metabolic process regulation of cellular process cellular biosynthetic process nucleolar chromatin organization negative regulation of cellular metabolic process protein-DNA complex organization cellular component organization chromatin organization organic substance biosynthetic process negative regulation of cellular process chromatin remodeling cellular component organization or biogenesis rDNA heterochromatin formation regulation of biosynthetic process heterochromatin formation protein-containing complex organization epigenetic regulation of gene expression cellular metabolic process regulation of cellular metabolic process gene expression macromolecule biosynthetic process negative regulation of cellular biosynthetic process regulation of cellular biosynthetic process regulation of gene expression negative regulation of gene expression nucleus organization organelle organization biosynthetic process negative regulation of biosynthetic process negative regulation of macromolecule biosynthetic process nucleolus organization facultative heterochromatin formation negative regulation of gene expression, epigenetic regulation of macromolecule biosynthetic process cellular process	intracellular anatomical structure cytoplasm cellular anatomical entity membrane-bounded organelle intracellular organelle organelle nucleus intracellular membrane-bounded organelle
B	Histone H4 peptide	DNA binding binding organic cyclic compound binding nucleic acid binding protein heterodimerization activity protein binding protein dimerization activity structural molecule activity structural constituent of chromatin	cellular biosynthetic process RNA metabolic process RNA biosynthetic process nucleobase-containing compound metabolic process DNA-templated transcription nucleic acid biosynthetic process organic substance metabolic process transcription by RNA polymerase I rRNA transcription organic substance biosynthetic process rRNA metabolic process nucleolar large rRNA transcription by RNA polymerase I cellular metabolic process primary metabolic process cellular biosynthetic process RNA metabolic process RNA biosynthetic process nucleobase-containing compound metabolic process DNA-templated transcription nucleic acid biosynthetic process organic substance metabolic process transcription by RNA polymerase I rRNA transcription organic substance biosynthetic process rRNA metabolic process nucleolar large rRNA transcription by RNA polymerase I cellular metabolic process primary metabolic process nucleobase-containing compound biosynthetic process gene expression macromolecule biosynthetic process nucleic acid metabolic process organic cyclic compound metabolic process biosynthetic process organic cyclic compound biosynthetic process ncRNA metabolic process metabolic process cellular process macromolecule metabolic process protein-containing complex organization protein-DNA complex assembly protein-DNA complex organization cellular component organization cellular component biogenesis cellular component assembly chromatin organization protein-containing complex assembly chromatin remodeling cellular component organization or biogenesis nucleosome assembly nucleosome organization regulation of cellular process regulation of primary metabolic process regulation of RNA metabolic process regulation of nucleobase-containing compound metabolic process regulation of RNA biosynthetic process regulation of biosynthetic process regulation of biological process biological regulation regulation of cellular metabolic process regulation of macromolecule metabolic process regulation of cellular biosynthetic process regulation of gene expression regulation of macromolecule biosynthetic process regulation of DNA-templated transcription regulation of metabolic process positive regulation of macromolecule biosynthetic process positive regulation of metabolic process positive regulation of macromolecule metabolic process positive regulation of nucleobase-containing compound metabolic process regulation of transcription by RNA polymerase I positive regulation of RNA metabolic process positive regulation of DNA-templated transcription positive regulation of biological process positive regulation of cellular metabolic process positive regulation of biosynthetic process positive regulation of transcription by RNA polymerase I positive regulation of cellular process positive regulation of RNA biosynthetic process positive regulation of cellular biosynthetic process	membrane-bounded organelle protein-containing complex intracellular anatomical structure nucleus membrane-enclosed lumen nuclear protein-containing complex transcription regulator complex intracellular membrane-bounded organelle cellular anatomical entity nucleolus intracellular organelle lumen intracellular organelle RNA polymerase I upstream activating factor complex RNA polymerase I transcription regulator complex membrane-bounded organelle protein-containing complex intracellular anatomical structure nucleus membrane-enclosed lumen nuclear protein-containing complex transcription regulator complex intracellular membrane-bounded organelle cellular anatomical entity nucleolus intracellular organelle lumen intracellular organelle RNA polymerase I upstream activating factor complex RNA polymerase I transcription regulator complex organelle lumen organelle intracellular non-membrane-bounded organelle nuclear lumen non-membrane-bounded organelle replication fork protection complex nuclear replication fork nuclear chromosome chromosome replication fork protein-DNA complex nucleosome chromatin

InterPro: Protein Family Classification InterPro Database Homepage

Chains	Accession	Name	Type
A	IPR026590	Sirtuin family, catalytic core domain	Domain
A	IPR017328	Sirtuin, class I	Family
A	IPR026591	Sirtuin, catalytic core small domain superfamily	Homologous Superfamily
A	IPR003000	Sirtuin family	Family
A	IPR029035	DHS-like NAD/FAD-binding domain superfamily	Homologous Superfamily
B	IPR009072	Histone-fold	Homologous Superfamily
B	IPR035425	CENP-T/Histone H4, histone fold	Domain
B	IPR001951	Histone H4	Family
B	IPR019809	Histone H4, conserved site	Conserved Site

Protein Modification Annotation

Modified Residue(s)
Chain	Residue(s)	Description
B	ALY	Parent Component: LYS RESID: AA0055 PSI-MOD : N6-acetyl-L-lysine MOD:00064

Structure Motif Annotation: Mechanism and Catalytic Site Atlas M-CSA Database Homepage

Chains	Enzyme Name	Description	Catalytic Residues
A	histone/protein deacetylase M-CSA #240	hST2, isolated from Saccharomyces cerevisiae, is a class III histone deacetylase (HDAC), though it also deacetylates other proteins. It belongs to the sirtuin (Sir2) family and catalyses the deacetylation of lysine residues from proteins using NAD+ as a co-substrate. The reaction produces a deacetylated lysine, nicotinamide and 2'-O-acetyl ADP-ribose. hST2 play roles in gene silencing and mediating life span extension. hST2 is of interest because its homologues in humans are potential drug targets for diseases associated with ageing, such as type-II diabetes, and Alzheimer's and Parkinson's diseases.	Defined by 7 residues: PRO:A-45 [auth A-42]ASP:A-46 [auth A-43]PHE:A-47 [auth A-44]ARG:A-48 [auth A-45]ASN:A-119 [auth A-116]ASP:A-121 [auth A-118]HIS:A-138 [auth A-135] \| Explore in 3D: M-CSA Motif Definition Search M-CSA Motif EC: 3.5.1 (PDB Primary Data) Search M-CSA Motif + EC 3.5.1

RCSB PDB Core Operations are funded by the National Science Foundation (DBI-1832184), 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 R01GM133198.