5V7I

Crystal structure of homo sapiens serine hydroxymethyltransferase 2 (mitochondrial) (SHMT2), in complex with glycine, PLP and folate-competitive pyrazolopyran inhibitor: 6-amino-4-isopropyl-3-methyl-4-(3-(pyrrolidin-1-yl)-5-(trifluoromethyl)phenyl)-1,4-dihydropyrano[2,3-c]pyrazole-5-carbonitrile

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
Protein Modification Annotation

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

Chains	Domain Info	Class	Fold	Superfamily	Family	Domain	Species	Provenance Source (Version)
A	d5v7ia_	Alpha and beta proteins (a/b)	PLP-dependent transferase-like	PLP-dependent transferases	GABA-aminotransferase-like	Serine hydroxymethyltransferase	Human (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)
B	d5v7ib_	Alpha and beta proteins (a/b)	PLP-dependent transferase-like	PLP-dependent transferases	GABA-aminotransferase-like	Serine hydroxymethyltransferase	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	PLP-dependent transferases	8036728	3000954	SCOP2B (2022-06-29)
B	SCOP2B Superfamily	PLP-dependent transferases	8036728	3000954	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	SHMT	e5v7iA1	A: a+b two layers	X: C-terminal domain in some PLP-dependent transferases (From Topology)	H: C-terminal domain in some PLP-dependent transferases (From Topology)	T: C-terminal domain in some PLP-dependent transferases	F: SHMT	ECOD (1.6)
A	Aminotran_5_N	e5v7iA2	A: a/b three-layered sandwiches	X: PLP-dependent transferases (From Topology)	H: PLP-dependent transferases (From Topology)	T: PLP-dependent transferases	F: Aminotran_5_N	ECOD (1.6)
B	SHMT	e5v7iB1	A: a+b two layers	X: C-terminal domain in some PLP-dependent transferases (From Topology)	H: C-terminal domain in some PLP-dependent transferases (From Topology)	T: C-terminal domain in some PLP-dependent transferases	F: SHMT	ECOD (1.6)
B	Aminotran_5_N	e5v7iB2	A: a/b three-layered sandwiches	X: PLP-dependent transferases (From Topology)	H: PLP-dependent transferases (From Topology)	T: PLP-dependent transferases	F: Aminotran_5_N	ECOD (1.6)

Domain Annotation: CATH CATH Database Homepage

Chain	Domain	Class	Architecture	Topology	Homology	Provenance Source (Version)
A	3.40.640.10	Alpha Beta	3-Layer(aba) Sandwich	Aspartate Aminotransferase	domain 2	CATH (4.3.0)
A	3.90.1150.10	Alpha Beta	Alpha-Beta Complex	Aspartate Aminotransferase, domain 1	Aspartate Aminotransferase, domain 1	CATH (4.3.0)
B	3.40.640.10	Alpha Beta	3-Layer(aba) Sandwich	Aspartate Aminotransferase	domain 2	CATH (4.3.0)
B	3.90.1150.10	Alpha Beta	Alpha-Beta Complex	Aspartate Aminotransferase, domain 1	Aspartate Aminotransferase, domain 1	CATH (4.3.0)

Protein Family Annotation Pfam Database Homepage

Chains	Accession	Name	Description	Comments	Source
A, B	PF00464	Serine hydroxymethyltransferase (SHMT)	Serine hydroxymethyltransferase	-	Domain

Gene Ontology: Gene Product Annotation Gene Ontology Database Homepage

Chains	Polymer	Molecular Function	Biological Process	Cellular Component
A, B	Serine hydroxymethyltransferase, mitochondrial	vitamin binding vitamin B6 binding pyridoxal phosphate binding ion binding binding organic cyclic compound binding anion binding heterocyclic compound binding small molecule binding chromatin binding amino acid binding threonine aldolase activity L-allo-threonine aldolase activity lyase activity vitamin binding vitamin B6 binding pyridoxal phosphate binding ion binding binding organic cyclic compound binding anion binding heterocyclic compound binding small molecule binding chromatin binding amino acid binding threonine aldolase activity L-allo-threonine aldolase activity lyase activity catalytic activity carbon-carbon lyase activity aldehyde-lyase activity transferase activity, transferring one-carbon groups glycine hydroxymethyltransferase activity transferase activity hydroxymethyl-, formyl- and related transferase activity identical protein binding protein binding	cellular component organization cellular component biogenesis cellular component assembly protein-containing complex organization protein complex oligomerization protein tetramerization protein-containing complex assembly cellular process cellular component organization or biogenesis protein homotetramerization protein homooligomerization folic acid-containing compound metabolic process tetrahydrofolate interconversion modified amino acid metabolic process cellular component organization cellular component biogenesis cellular component assembly protein-containing complex organization protein complex oligomerization protein tetramerization protein-containing complex assembly cellular process cellular component organization or biogenesis protein homotetramerization protein homooligomerization folic acid-containing compound metabolic process tetrahydrofolate interconversion modified amino acid metabolic process metabolic process small molecule metabolic process tetrahydrofolate metabolic process pteridine-containing compound metabolic process one-carbon metabolic process protein deubiquitination protein K63-linked deubiquitination primary metabolic process protein modification by small protein removal macromolecule modification protein metabolic process macromolecule metabolic process post-translational protein modification protein modification process protein modification by small protein conjugation or removal serine family amino acid metabolic process oxoacid metabolic process amino acid metabolic process organic acid metabolic process organic acid biosynthetic process alpha-amino acid metabolic process carboxylic acid biosynthetic process small molecule biosynthetic process carboxylic acid metabolic process L-amino acid biosynthetic process L-serine metabolic process L-serine biosynthetic process L-amino acid metabolic process proteinogenic amino acid metabolic process amino acid biosynthetic process biosynthetic process proteinogenic amino acid biosynthetic process serine family amino acid biosynthetic process alpha-amino acid biosynthetic 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 positive regulation of cellular process mitochondrial translation regulation of mitochondrial gene expression mitochondrial gene expression regulation of primary metabolic process post-transcriptional regulation of gene expression regulation of biosynthetic process regulation of protein metabolic process regulation of macromolecule metabolic process gene expression translation macromolecule biosynthetic process regulation of gene expression regulation of mitochondrial translation regulation of translation regulation of macromolecule biosynthetic process regulation of metabolic process biological process involved in interspecies interaction between organisms response to stimulus immune response response to other organism defense response response to cytokine defense response to symbiont response to external stimulus response to biotic stimulus response to peptide response to chemical immune system process defense response to other organism response to stress innate immune response response to external biotic stimulus response to type I interferon aerobic respiration cellular respiration oxidative phosphorylation energy derivation by oxidation of organic compounds regulation of generation of precursor metabolites and energy generation of precursor metabolites and energy regulation of cellular respiration regulation of aerobic respiration regulation of oxidative phosphorylation glycine metabolic process glycine biosynthetic process glycine biosynthetic process from serine	membrane-bounded organelle intracellular organelle cellular anatomical structure intracellular anatomical structure mitochondrion organelle cytoplasm intracellular membrane-bounded organelle mitochondrial membrane organelle inner membrane membrane mitochondrial inner membrane organelle envelope mitochondrial envelope membrane-bounded organelle intracellular organelle cellular anatomical structure intracellular anatomical structure mitochondrion organelle cytoplasm intracellular membrane-bounded organelle mitochondrial membrane organelle inner membrane membrane mitochondrial inner membrane organelle envelope mitochondrial envelope organelle membrane extracellular exosome extracellular vesicle extracellular organelle extracellular region extracellular space vesicle extracellular membrane-bounded organelle cytoskeleton membraneless organelle intracellular membraneless organelle microtubule cytoskeleton protein-containing complex BRISC complex nucleus nuclear protein-containing complex membrane-enclosed lumen nucleoid mitochondrial matrix intracellular organelle lumen organelle lumen mitochondrial nucleoid

InterPro: Protein Family Classification InterPro Database Homepage

Chains	Accession	Name	Type
A, B	IPR019798	Serine hydroxymethyltransferase, pyridoxal phosphate binding site	Binding Site
A, B	IPR015421	Pyridoxal phosphate-dependent transferase, major domain	Homologous Superfamily
A, B	IPR015422	Pyridoxal phosphate-dependent transferase, small domain	Homologous Superfamily
A, B	IPR039429	Serine hydroxymethyltransferase-like domain	Domain
A, B	IPR001085	Serine hydroxymethyltransferase	Family
A, B	IPR015424	Pyridoxal phosphate-dependent transferase	Homologous Superfamily
A, B	IPR049943	Serine hydroxymethyltransferase-like	Family

Pharos: Disease Associations Pharos Homepage Annotation

Chains	Drug Target	Associated Disease
A, B	Pharos: P34897	non-small cell lung carcinoma nasopharyngeal carcinoma osteosarcoma plasma cell myeloma Sjogren syndrome abdominal aortic aneurysm astrocytic tumor breast cancer colorectal cancer heart disease lung cancer malignant glioma ovarian cancer Plasmodium vivax malaria acute myeloid leukemia non-small cell lung carcinoma nasopharyngeal carcinoma osteosarcoma plasma cell myeloma Sjogren syndrome abdominal aortic aneurysm astrocytic tumor breast cancer colorectal cancer heart disease lung cancer malignant glioma ovarian cancer Plasmodium vivax malaria acute myeloid leukemia atopic eczema cardiomyopathy diabetes mellitus large cell medulloblastoma malignant colon neoplasm medulloblastoma oligodendroglioma pancreatic ductal adenocarcinoma psoriasis adrenal cortex carcinoma autism spectrum disorder colorectal adenoma glioblastoma lung adenocarcinoma malignant ependymoma

Protein Modification Annotation

Modified Residue(s)
Chain	Residue(s)	Description
A, B	LLP	Parent Component: LYS RESID: AA0119 PSI-MOD : N6-pyridoxal phosphate-L-lysine MOD:00128

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.