1ROZ

Deoxyhypusine synthase holoenzyme in its low ionic strength, high pH crystal form

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
Pharos: Disease Associations
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	d1roza_	Alpha and beta proteins (a/b)	DHS-like NAD/FAD-binding domain	DHS-like NAD/FAD-binding domain	Deoxyhypusine synthase, DHS	Deoxyhypusine synthase, DHS	human (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)
B	d1rozb_	Alpha and beta proteins (a/b)	DHS-like NAD/FAD-binding domain	DHS-like NAD/FAD-binding domain	Deoxyhypusine synthase, DHS	Deoxyhypusine synthase, DHS	human (Homo sapiens ) [TaxId: 9606 ],	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	8044242	3001728	SCOP2B (2022-06-29)
B	SCOP2B Superfamily	DHS-like NAD/FAD-binding domain	8044242	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	DS	e1rozA1	A: a/b three-layered sandwiches	X: Rossmann-like	H: Rossmann-related	T: DHS-like NAD/FAD-binding domain	F: DS	ECOD (1.6)
B	DS	e1rozB1	A: a/b three-layered sandwiches	X: Rossmann-like	H: Rossmann-related	T: DHS-like NAD/FAD-binding domain	F: DS	ECOD (1.6)

Domain Annotation: CATH CATH Database Homepage

Chain	Domain	Class	Architecture	Topology	Homology	Provenance Source (Version)
A	3.40.910.10	Alpha Beta	3-Layer(aba) Sandwich	Deoxyhypusine Synthase	Deoxyhypusine synthase	CATH (4.3.0)
B	3.40.910.10	Alpha Beta	3-Layer(aba) Sandwich	Deoxyhypusine Synthase	Deoxyhypusine synthase	CATH (4.3.0)

Protein Family Annotation Pfam Database Homepage

Chains	Accession	Name	Description	Comments	Source
A, B	PF01916	Deoxyhypusine synthase (DS)	Deoxyhypusine synthase	Eukaryotic initiation factor 5A (eIF-5A) contains an unusual amino acid, hypusine [N epsilon-(4-aminobutyl-2-hydroxy)lysine]. The first step in the post-translational formation of hypusine is catalysed by the enzyme deoxyhypusine synthase (DS) EC:1.1 ...	Eukaryotic initiation factor 5A (eIF-5A) contains an unusual amino acid, hypusine [N epsilon-(4-aminobutyl-2-hydroxy)lysine]. The first step in the post-translational formation of hypusine is catalysed by the enzyme deoxyhypusine synthase (DS) EC:1.1.1.249. The modified version of eIF-5A, and DS, are required for eukaryotic cell proliferation [1].	Domain

Gene Ontology: Gene Product Annotation Gene Ontology Database Homepage

Chains	Polymer	Molecular Function	Biological Process	Cellular Component
A, B	Deoxyhypusine synthase	deoxyhypusine synthase activity transferase activity transferase activity, transferring alkyl or aryl (other than methyl) groups catalytic activity identical protein binding protein binding binding	regulation of biological process cell population proliferation regulation of cellular process positive regulation of cell population proliferation regulation of cell population proliferation biological regulation positive regulation of biological process cellular process positive regulation of cellular process spermidine catabolic process catabolic process polyamine metabolic process biogenic amine catabolic process amine metabolic process regulation of biological process cell population proliferation regulation of cellular process positive regulation of cell population proliferation regulation of cell population proliferation biological regulation positive regulation of biological process cellular process positive regulation of cellular process spermidine catabolic process catabolic process polyamine metabolic process biogenic amine catabolic process amine metabolic process spermidine metabolic process metabolic process polyamine catabolic process biogenic amine metabolic process amine catabolic process peptidyl-lysine modification to peptidyl-hypusine peptidyl-lysine modification primary metabolic process gene expression macromolecule biosynthetic process protein maturation biosynthetic process macromolecule modification peptidyl-amino acid modification protein metabolic process macromolecule metabolic process protein modification process multicellular organismal process regulation of leukocyte activation regulation of cell activation positive regulation of cell activation T cell activation lymphocyte proliferation positive regulation of leukocyte activation regulation of immune system process positive regulation of immune system process regulation of leukocyte proliferation positive regulation of T cell activation positive regulation of lymphocyte proliferation positive regulation of T cell proliferation mononuclear cell proliferation regulation of leukocyte cell-cell adhesion positive regulation of leukocyte proliferation positive regulation of multicellular organismal process positive regulation of leukocyte cell-cell adhesion lymphocyte activation leukocyte proliferation leukocyte cell-cell adhesion leukocyte activation positive regulation of cell-cell adhesion positive regulation of lymphocyte activation cell adhesion cell-cell adhesion positive regulation of mononuclear cell proliferation regulation of multicellular organismal process regulation of cell-cell adhesion T cell proliferation regulation of lymphocyte proliferation positive regulation of cell adhesion regulation of cell adhesion cell activation regulation of T cell activation regulation of T cell proliferation immune system process regulation of mononuclear cell proliferation regulation of lymphocyte activation chemical homeostasis homeostatic process glucose homeostasis carbohydrate homeostasis translation	cellular anatomical structure intracellular anatomical structure cytoplasm cytosol

InterPro: Protein Family Classification InterPro Database Homepage

Chains	Accession	Name	Type
A, B	IPR036982	Deoxyhypusine synthase superfamily	Homologous Superfamily
A, B	IPR029035	DHS-like NAD/FAD-binding domain superfamily	Homologous Superfamily
A, B	IPR002773	Deoxyhypusine synthase	Family

Pharos: Disease Associations Pharos Homepage Annotation

Chains	Drug Target	Associated Disease
A, B	Pharos: P49366	acute myeloid leukemia pancreatic ductal adenocarcinoma pulmonary emphysema diabetes mellitus plasma cell myeloma subependymal giant cell astrocytoma osteosarcoma psoriasis

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

Chains	Enzyme Name	Description	Catalytic Residues
A, B	deoxyhypusine synthase M-CSA #687	Deoxyhypusine is a highly rare posttranslational modification that occurs in eukaryotes where the it is vital for the formation of the initiation factor eIF5A. The enzyme carrying the reaction out is deoxyhypusine synthase which is able to transfer a butylamine moiety from spermidine to a lysine in eIF5A, using NAD as a cofactor. Since active eIF5A is required for tumour cell proliferation, design of inhibitors for this enzyme could prove useful in the treatment of certain cancers. The high specificity of the enzyme is also of interest, because the only incidence of this modification in eukaryotic proteins appears to be in this particular case.	Defined by 3 residues: HIS:A-288LYS:A-329GLU:B_2-137 \| Explore in 3D: M-CSA Motif Definition Search M-CSA Motif EC: 2.5.1.46 (PDB Primary Data) Search M-CSA Motif + EC 2.5.1.46

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.