4BZC

Crystal structure of the tetrameric dGTP-bound wild type SAMHD1 catalytic core

External Resource: Annotation

Domain Annotation: ECOD Classification
Domain Annotation: CATH
Protein Family Annotation
Gene Ontology: Gene Product Annotation
InterPro: Protein Family Classification
Pharos: Disease Associations
Structure Motif: Primary M-CSA Annotation

Domain Annotation: ECOD Classification ECOD Database Homepage

Chains	Family Name	Domain Identifier	Architecture	Possible Homology	Homology	Topology	Family	Provenance Source (Version)
A	HD	e4bzcA1	A: alpha complex topology	X: PDEase-like	H: HD-domain/PDEase-like (From Topology)	T: HD-domain/PDEase-like	F: HD	ECOD (1.6)
B	HD	e4bzcB1	A: alpha complex topology	X: PDEase-like	H: HD-domain/PDEase-like (From Topology)	T: HD-domain/PDEase-like	F: HD	ECOD (1.6)
C	HD	e4bzcC1	A: alpha complex topology	X: PDEase-like	H: HD-domain/PDEase-like (From Topology)	T: HD-domain/PDEase-like	F: HD	ECOD (1.6)
D	HD	e4bzcD1	A: alpha complex topology	X: PDEase-like	H: HD-domain/PDEase-like (From Topology)	T: HD-domain/PDEase-like	F: HD	ECOD (1.6)

Domain Annotation: CATH CATH Database Homepage

Chain	Domain	Class	Architecture	Topology	Homology	Provenance Source (Version)
A	1.10.3210.10	Mainly Alpha	Orthogonal Bundle	Hypothetical protein af1432	Hypothetical protein af1432	CATH (4.3.0)
B	1.10.3210.10	Mainly Alpha	Orthogonal Bundle	Hypothetical protein af1432	Hypothetical protein af1432	CATH (4.3.0)
C	1.10.3210.10	Mainly Alpha	Orthogonal Bundle	Hypothetical protein af1432	Hypothetical protein af1432	CATH (4.3.0)
D	1.10.3210.10	Mainly Alpha	Orthogonal Bundle	Hypothetical protein af1432	Hypothetical protein af1432	CATH (4.3.0)

Protein Family Annotation Pfam Database Homepage

Chains	Accession	Name	Description	Comments	Source
A, B, C, D	PF01966	HD domain (HD)	HD domain	-	Family

Gene Ontology: Gene Product Annotation Gene Ontology Database Homepage

Chains	Polymer	Molecular Function	Biological Process	Cellular Component
A, B, C, D	DEOXYNUCLEOSIDE TRIPHOSPHATE TRIPHOSPHOHYDROLASE SAMHD1	binding organic cyclic compound binding nucleic acid binding dGTP binding guanyl nucleotide binding deoxyribonucleotide binding nucleotide binding purine deoxyribonucleotide binding nucleoside phosphate binding ion binding purine nucleotide binding anion binding guanyl deoxyribonucleotide binding heterocyclic compound binding binding organic cyclic compound binding nucleic acid binding dGTP binding guanyl nucleotide binding deoxyribonucleotide binding nucleotide binding purine deoxyribonucleotide binding nucleoside phosphate binding ion binding purine nucleotide binding anion binding guanyl deoxyribonucleotide binding heterocyclic compound binding carbohydrate derivative binding small molecule binding phosphoric ester hydrolase activity triphosphoric monoester hydrolase activity dGTPase activity hydrolase activity, acting on ester bonds hydrolase activity catalytic activity RNA binding GTP binding guanyl ribonucleotide binding purine ribonucleotide binding purine ribonucleoside triphosphate binding ribonucleotide binding nuclease activity catalytic activity, acting on RNA catalytic activity, acting on a nucleic acid RNA nuclease activity deoxynucleoside triphosphate hydrolase activity cation binding transition metal ion binding zinc ion binding metal ion binding identical protein binding protein binding DNA binding single-stranded DNA binding	cellular response to stimulus cellular response to stress response to stimulus DNA damage response response to stress cellular process immune response immune system process nucleoside phosphate metabolic process carbohydrate derivative catabolic process deoxyribonucleotide catabolic process catabolic process carbohydrate derivative metabolic process organophosphate catabolic process cellular response to stimulus cellular response to stress response to stimulus DNA damage response response to stress cellular process immune response immune system process nucleoside phosphate metabolic process carbohydrate derivative catabolic process deoxyribonucleotide catabolic process catabolic process carbohydrate derivative metabolic process organophosphate catabolic process primary metabolic process nucleoside phosphate catabolic process nucleotide metabolic process nucleobase-containing compound catabolic process nucleobase-containing compound metabolic process deoxyribonucleotide metabolic process organophosphate metabolic process nucleobase-containing small molecule metabolic process phosphate-containing compound metabolic process metabolic process small molecule metabolic process phosphorus metabolic process nucleotide catabolic process regulation of cellular process regulation of type I interferon-mediated signaling pathway negative regulation of biological process response to cytokine regulation of signal transduction response to biotic stimulus cell communication interferon-mediated signaling pathway cellular response to type I interferon cellular response to cytokine stimulus regulation of immune system process signal transduction regulation of biological process response to other organism regulation of innate immune response negative regulation of immune response response to external stimulus regulation of response to cytokine stimulus negative regulation of response to cytokine stimulus regulation of response to stimulus response to chemical defense response to other organism negative regulation of response to external stimulus negative regulation of defense response regulation of immune response response to type I interferon regulation of defense response regulation of response to biotic stimulus biological process involved in interspecies interaction between organisms regulation of response to external stimulus negative regulation of response to biotic stimulus negative regulation of signaling signaling negative regulation of cell communication cytokine-mediated signaling pathway regulation of response to stress negative regulation of cellular process innate immune response response to external biotic stimulus regulation of signaling cell surface receptor signaling pathway negative regulation of response to stimulus defense response regulation of cytokine-mediated signaling pathway biological regulation defense response to symbiont negative regulation of signal transduction response to peptide negative regulation of immune system process negative regulation of cytokine-mediated signaling pathway type I interferon-mediated signaling pathway regulation of cell communication negative regulation of type I interferon-mediated signaling pathway negative regulation of innate immune response protein-containing complex organization protein homotetramerization cellular component organization cellular component biogenesis cellular component assembly protein complex oligomerization protein tetramerization protein-containing complex assembly protein homooligomerization cellular component organization or biogenesis immune system development developmental process production of molecular mediator of immune response multicellular organismal process immunoglobulin production somatic diversification of immune receptors via somatic mutation gene expression macromolecule biosynthetic process somatic diversification of immunoglobulins multicellular organism development biosynthetic process anatomical structure development somatic diversification of immune receptors macromolecule metabolic process somatic hypermutation of immunoglobulin genes system development nucleoside triphosphate catabolic process purine nucleoside triphosphate catabolic process purine deoxyribonucleoside triphosphate metabolic process dGTP metabolic process deoxyribose phosphate catabolic process purine nucleotide metabolic process purine deoxyribonucleoside triphosphate catabolic process deoxyribonucleoside triphosphate metabolic process purine nucleoside triphosphate metabolic process purine nucleotide catabolic process purine deoxyribonucleotide catabolic process 2'-deoxyribonucleotide metabolic process purine-containing compound catabolic process deoxyribonucleoside triphosphate catabolic process deoxyribose phosphate metabolic process purine-containing compound metabolic process purine deoxyribonucleotide metabolic process nucleoside triphosphate metabolic process dGTP catabolic process DNA-templated DNA replication DNA-templated DNA replication maintenance of fidelity DNA metabolic process nucleic acid metabolic process DNA replication DNA strand resection involved in replication fork processing replication fork processing double-strand break repair DNA recombination recombinational repair double-strand break repair via homologous recombination DNA repair dATP metabolic process dATP catabolic process defense response to virus response to virus	cell periphery cellular anatomical structure plasma membrane membrane membrane-bounded organelle intracellular anatomical structure nucleus membrane-enclosed lumen intracellular membrane-bounded organelle intracellular organelle lumen intracellular organelle nucleoplasm organelle lumen organelle cell periphery cellular anatomical structure plasma membrane membrane membrane-bounded organelle intracellular anatomical structure nucleus membrane-enclosed lumen intracellular membrane-bounded organelle intracellular organelle lumen intracellular organelle nucleoplasm organelle lumen organelle nuclear lumen site of double-strand break membraneless organelle site of DNA damage intracellular membraneless organelle chromosome tetraspanin-enriched microdomain

InterPro: Protein Family Classification InterPro Database Homepage

Chains	Accession	Name	Type
A, B, C, D	IPR050135	Deoxyguanosinetriphosphate triphosphohydrolase-like	Family
A, B, C, D	IPR006674	HD domain	Domain
A, B, C, D	IPR003607	HD/PDEase domain	Domain
A, B, C, D	IPR013761	Sterile alpha motif/pointed domain superfamily	Homologous Superfamily
A, B, C, D	IPR001660	Sterile alpha motif domain	Domain

Pharos: Disease Associations Pharos Homepage Annotation

Chains	Drug Target	Associated Disease
A, B, C, D	Pharos: Q9Y3Z3	Aicardi-Goutieres syndrome chilblain lupus Aicardi-Goutieres syndrome 5 chilblain lupus 2 mitochondrial DNA depletion syndrome, hepatocerebral form HIV infectious disease interstitial cystitis leukodystrophy lung carcinoma adenoma Mitochondrial Diseases Aicardi-Goutieres syndrome 2 non-small cell lung carcinoma astrocytic tumor ovarian cancer Aicardi-Goutieres syndrome chilblain lupus Aicardi-Goutieres syndrome 5 chilblain lupus 2 mitochondrial DNA depletion syndrome, hepatocerebral form HIV infectious disease interstitial cystitis leukodystrophy lung carcinoma adenoma Mitochondrial Diseases Aicardi-Goutieres syndrome 2 non-small cell lung carcinoma astrocytic tumor ovarian cancer pancreatic intraductal papillary-mucinous neoplasm cutaneous lupus erythematosus pituitary cancer Emery-Dreifuss muscular dystrophy subependymal giant cell astrocytoma gastric carcinoma IgA glomerulonephritis juvenile dermatomyositis limb-girdle muscular dystrophy malignant glioma oligodendroglioma B-cell chronic lymphocytic leukemia pancreatic ductal adenocarcinoma pancreatic intraductal papillary-mucinous neoplasm with low grade dysplasia pseudo-TORCH syndrome tuberculosis glioblastoma intellectual disability large cell medulloblastoma lung cancer medulloblastoma Aicardi-Goutieres syndrome 1 myopathy osteosarcoma cerebrovascular disorder pancreatic intraductal papillary-mucinous carcinoma Crohn disease pilocytic astrocytoma Duchenne muscular dystrophy Sjogren syndrome facioscapulohumeral muscular dystrophy ulcerative colitis

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

Chains	Enzyme Name	Description	Catalytic Residues
A	deoxynucleoside triphosphate triphosphohydrolase SAMHD1 M-CSA #994	Sterile α-motif/histidine-aspartate domain-containing protein (SAMHD1) is a homo-tetrameric GTP/dGTP-activated dNTPase which catalyses the conversion of dNTP into 2'-deoxynucleoside and triphosphate. The enzyme interconverts between an inactive monomeric or dimeric form and a dGTP/GTP-induced active tetrameric form. SAMHD1 is ubiquitously expressed in various human organs. SAMHD1 plays an important role in human innate immunity, autoimmunity and cell cycle control. It blocks retroviral infections (including HIV) and transposition of endogenous retroelements as well as preventing infections from certain DNA viruses.	Defined by 12 residues: GLN:A-73 [auth A-149]HIS:A-91 [auth A-167]HIS:A-130 [auth A-206]ASP:A-131 [auth A-207]HIS:A-134 [auth A-210]HIS:A-139 [auth A-215]ASP:A-142 [auth A-218]HIS:A-157 [auth A-233]ASP:A-235 [auth A-311]LYS:A-236 [auth A-312]ASP:A-243 [auth A-319]ARG:A-290 [auth A-366] \| Explore in 3D: M-CSA Motif Definition Up to 10 residues are supported for Structure Motif searching, this motif has 12 residues. EC: 3.1.5 (PDB Primary Data)

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.