4C4G

Structure-based design of orally bioavailable pyrrolopyridine inhibitors of the mitotic kinase MPS1

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	d4c4ga1	Alpha and beta proteins (a+b)	Protein kinase-like (PK-like)	Protein kinase-like (PK-like)	automated matches	automated matches	HUMAN (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)
A	d4c4ga2	Artifacts	Tags	Tags	Tags	N-terminal Tags	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	Protein kinase-like (PK-like)	8076791	3000066	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	Pkinase_Tyr	e4c4gA1	A: a+b complex topology	X: Protein kinase/SAICAR synthase/ATP-grasp (From Homology)	H: Protein kinase/SAICAR synthase/ATP-grasp	T: Protein kinase	F: Pkinase_Tyr	ECOD (1.6)

Domain Annotation: CATH CATH Database Homepage

Chain	Domain	Class	Architecture	Topology	Homology	Provenance Source (Version)
A	3.30.200.20	Alpha Beta	2-Layer Sandwich	Phosphorylase Kinase	domain 1	CATH (4.3.0)
A	1.10.510.10	Mainly Alpha	Orthogonal Bundle	Transferase(Phosphotransferase)	domain 1	CATH (4.3.0)

Protein Family Annotation Pfam Database Homepage

Chains	Accession	Name	Description	Comments	Source
A	PF00069	Protein kinase domain (Pkinase)	Protein kinase domain	-	Domain

Gene Ontology: Gene Product Annotation Gene Ontology Database Homepage

Chains	Polymer	Molecular Function	Biological Process	Cellular Component
A	DUAL SPECIFICITY PROTEIN KINASE TTK	protein serine/threonine/tyrosine kinase activity catalytic activity, acting on a protein kinase activity protein kinase activity transferase activity catalytic activity phosphotransferase activity, alcohol group as acceptor transferase activity, transferring phosphorus-containing groups protein serine kinase activity binding kinetochore binding protein tyrosine kinase activity adenyl ribonucleotide binding nucleotide binding protein serine/threonine/tyrosine kinase activity catalytic activity, acting on a protein kinase activity protein kinase activity transferase activity catalytic activity phosphotransferase activity, alcohol group as acceptor transferase activity, transferring phosphorus-containing groups protein serine kinase activity binding kinetochore binding protein tyrosine kinase activity adenyl ribonucleotide binding nucleotide binding purine ribonucleotide binding purine ribonucleoside triphosphate binding nucleoside phosphate binding ion binding purine nucleotide binding organic cyclic compound binding anion binding adenyl nucleotide binding ATP binding heterocyclic compound binding carbohydrate derivative binding ribonucleotide binding small molecule binding protein serine/threonine kinase activity identical protein binding protein binding	meiotic chromosome segregation sexual reproduction reproductive process organelle fission meiotic cell cycle multicellular organismal reproductive process female gamete generation meiotic cell cycle process gamete generation cellular component organization nuclear division organelle organization female meiotic nuclear division nuclear chromosome segregation meiotic chromosome segregation sexual reproduction reproductive process organelle fission meiotic cell cycle multicellular organismal reproductive process female gamete generation meiotic cell cycle process gamete generation cellular component organization nuclear division organelle organization female meiotic nuclear division nuclear chromosome segregation meiotic nuclear division cellular process cellular component organization or biogenesis cell cycle female meiosis chromosome segregation chromosome segregation cell cycle process protein localization cellular localization protein localization to chromosome, centromeric region localization protein localization to kinetochore protein localization to chromosome protein localization to condensed chromosome protein localization to organelle cellular macromolecule localization macromolecule localization cellular response to stimulus regulation of cellular process regulation of cell cycle phase transition response to stimulus negative regulation of biological process spindle checkpoint signaling negative regulation of cell cycle regulation of mitotic nuclear division intracellular signal transduction negative regulation of mitotic cell cycle cell communication negative regulation of mitotic sister chromatid segregation negative regulation of chromosome organization negative regulation of cell cycle phase transition mitotic spindle checkpoint signaling signal transduction mitotic sister chromatid separation negative regulation of sister chromatid segregation mitotic spindle assembly checkpoint signaling regulation of biological process negative regulation of cellular component organization regulation of cell cycle process sister chromatid segregation regulation of chromosome organization regulation of organelle organization regulation of mitotic cell cycle phase transition regulation of mitotic sister chromatid segregation mitotic cell cycle process regulation of chromosome separation negative regulation of mitotic nuclear division regulation of chromosome segregation regulation of cellular component organization regulation of mitotic sister chromatid separation regulation of metaphase/anaphase transition of cell cycle signaling spindle assembly checkpoint signaling cell cycle phase transition regulation of mitotic metaphase/anaphase transition mitotic cell cycle regulation of mitotic cell cycle negative regulation of cellular process mitotic sister chromatid segregation negative regulation of mitotic metaphase/anaphase transition regulation of cell cycle negative regulation of chromosome separation mitotic nuclear division negative regulation of mitotic cell cycle phase transition biological regulation chromosome organization negative regulation of cell cycle process cell cycle checkpoint signaling mitotic cell cycle checkpoint signaling negative regulation of chromosome segregation chromosome separation negative regulation of organelle organization negative regulation of nuclear division regulation of sister chromatid segregation negative regulation of mitotic sister chromatid separation regulation of nuclear division negative regulation of metaphase/anaphase transition of cell cycle metaphase/anaphase transition of mitotic cell cycle metaphase/anaphase transition of cell cycle mitotic cell cycle phase transition protein localization to microtubule cytoskeleton protein localization to meiotic spindle protein localization to cytoskeleton protein localization to meiotic spindle midzone cell population proliferation positive regulation of cell population proliferation regulation of cell population proliferation positive regulation of biological process positive regulation of cellular process microtubule cytoskeleton organization mitotic spindle organization microtubule-based process cytoskeleton organization microtubule cytoskeleton organization involved in mitosis spindle organization establishment of organelle localization mitotic metaphase chromosome alignment metaphase chromosome alignment repair of kinetochore microtubule attachment defect chromosome localization organelle localization establishment of localization in cell repair of mitotic kinetochore microtubule attachment defect establishment of localization establishment of chromosome localization regulation of reproductive process meiotic spindle assembly checkpoint signaling regulation of metaphase/anaphase transition of meiotic cell cycle regulation of meiotic cell cycle negative regulation of meiotic chromosome separation negative regulation of meiotic cell cycle phase transition negative regulation of meiotic cell cycle meiotic spindle checkpoint signaling regulation of meiotic chromosome separation negative regulation of metaphase/anaphase transition of meiotic cell cycle metaphase/anaphase transition of meiotic cell cycle meiotic chromosome separation regulation of meiotic cell cycle phase transition meiotic cell cycle checkpoint signaling meiotic cell cycle phase transition negative regulation of reproductive process	cellular anatomical structure membrane intracellular anatomical structure cytoplasm intracellular membraneless organelle chromosome chromosomal region kinetochore intracellular organelle organelle membraneless organelle chromosome, centromeric region condensed chromosome, centromeric region supramolecular complex cellular anatomical structure membrane intracellular anatomical structure cytoplasm intracellular membraneless organelle chromosome chromosomal region kinetochore intracellular organelle organelle membraneless organelle chromosome, centromeric region condensed chromosome, centromeric region supramolecular complex condensed chromosome cytoskeleton spindle microtubule cytoskeleton membrane-bounded organelle nucleus intracellular membrane-bounded organelle

InterPro: Protein Family Classification InterPro Database Homepage

Chains	Accession	Name	Type
A	IPR017441	Protein kinase, ATP binding site	Binding Site
A	IPR011990	Tetratricopeptide-like helical domain superfamily	Homologous Superfamily
A	IPR000719	Protein kinase domain	Domain
A	IPR011009	Protein kinase-like domain superfamily	Homologous Superfamily
A	IPR027084	Protein kinase Mps1 family, catalytic domain	Domain
A	IPR008271	Serine/threonine-protein kinase, active site	Active Site

Pharos: Disease Associations Pharos Homepage Annotation

Chains	Drug Target	Associated Disease
A	Pharos: P33981	polycystic ovary syndrome non-small cell lung carcinoma malignant glioma medulloblastoma ovarian cancer pilocytic astrocytoma psoriasis adrenal cortex carcinoma breast cancer endometriosis hepatocellular carcinoma Interstitial fibrosis large cell medulloblastoma malignant colon neoplasm malignant mesothelioma polycystic ovary syndrome non-small cell lung carcinoma malignant glioma medulloblastoma ovarian cancer pilocytic astrocytoma psoriasis adrenal cortex carcinoma breast cancer endometriosis hepatocellular carcinoma Interstitial fibrosis large cell medulloblastoma malignant colon neoplasm malignant mesothelioma nasopharyngeal carcinoma pancreatic intraductal papillary-mucinous carcinoma atopic eczema breast carcinoma esophageal adenocarcinoma idiopathic pulmonary fibrosis interstitial lung disease lung adenocarcinoma malignant ependymoma malignant pancreatic neoplasm pancreatic intraductal papillary-mucinous neoplasm primitive neuroectodermal tumor Sjogren syndrome atypical teratoid rhabdoid tumor ductal breast carcinoma in situ glioblastoma IgA glomerulonephritis invasive ductal breast carcinoma lung cancer

Protein Modification Annotation

Modified Residue(s)
Chain	Residue(s)	Description
A	TPO	Parent Component: THR RESID: AA0038 PSI-MOD : O-phospho-L-threonine MOD:00047

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.