4ZYC

Discovery of dihydroisoquinolinone derivatives as novel inhibitors of the p53-MDM2 interaction with a distinct binding mode: Hdm2 (MDM2) complexed with cpd5

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

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

Chains	Domain Info	Class	Fold	Superfamily	Family	Domain	Species	Provenance Source (Version)
A	d4zyca_	All alpha proteins	SWIB/MDM2 domain	SWIB/MDM2 domain	SWIB/MDM2 domain	MDM2	Human (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)
B	d4zycb_	All alpha proteins	SWIB/MDM2 domain	SWIB/MDM2 domain	SWIB/MDM2 domain	MDM2	Human (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)
C	d4zycc_	All alpha proteins	SWIB/MDM2 domain	SWIB/MDM2 domain	SWIB/MDM2 domain	MDM2	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	SWIB/MDM2 domain-like	8037458	3000287	SCOP2B (2022-06-29)
B	SCOP2B Superfamily	SWIB/MDM2 domain-like	8037458	3000287	SCOP2B (2022-06-29)
C	SCOP2B Superfamily	SWIB/MDM2 domain-like	8037458	3000287	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	SWIB	e4zycA1	A: alpha arrays	X: SWIB/MDM2 domain (From Topology)	H: SWIB/MDM2 domain (From Topology)	T: SWIB/MDM2 domain	F: SWIB	ECOD (1.6)
B	SWIB	e4zycB1	A: alpha arrays	X: SWIB/MDM2 domain (From Topology)	H: SWIB/MDM2 domain (From Topology)	T: SWIB/MDM2 domain	F: SWIB	ECOD (1.6)
C	SWIB	e4zycC1	A: alpha arrays	X: SWIB/MDM2 domain (From Topology)	H: SWIB/MDM2 domain (From Topology)	T: SWIB/MDM2 domain	F: SWIB	ECOD (1.6)

Domain Annotation: CATH CATH Database Homepage

Chain	Domain	Class	Architecture	Topology	Homology	Provenance Source (Version)
A	1.10.245.10	Mainly Alpha	Orthogonal Bundle	MDM2	SWIB/MDM2 domain	CATH (4.3.0)
B	1.10.245.10	Mainly Alpha	Orthogonal Bundle	MDM2	SWIB/MDM2 domain	CATH (4.3.0)
C	1.10.245.10	Mainly Alpha	Orthogonal Bundle	MDM2	SWIB/MDM2 domain	CATH (4.3.0)

Protein Family Annotation Pfam Database Homepage

Chains	Accession	Name	Description	Comments	Source
A, B, C	PF02201	SWIB/MDM2 domain (SWIB)	SWIB/MDM2 domain	This family includes the SWIB domain and the MDM2 domain [1]. The p53-associated protein (MDM2) is an inhibitor of the p53 tumour suppressor gene binding the transactivation domain and down regulating the ability of p53 to activate transcription. Thi ...	This family includes the SWIB domain and the MDM2 domain [1]. The p53-associated protein (MDM2) is an inhibitor of the p53 tumour suppressor gene binding the transactivation domain and down regulating the ability of p53 to activate transcription. This family contains the p53 binding domain of MDM2 [2].	Domain

Gene Ontology: Gene Product Annotation Gene Ontology Database Homepage

Chains	Polymer	Molecular Function	Biological Process	Cellular Component
A, B, C	E3 ubiquitin-protein ligase Mdm2	aminoacyltransferase activity ubiquitin-like protein transferase activity catalytic activity, acting on a protein acyltransferase activity SUMO transferase activity transferase activity catalytic activity ubiquitin protein ligase binding protein binding binding ubiquitin-like protein ligase binding enzyme binding ligase activity protein domain specific binding aminoacyltransferase activity ubiquitin-like protein transferase activity catalytic activity, acting on a protein acyltransferase activity SUMO transferase activity transferase activity catalytic activity ubiquitin protein ligase binding protein binding binding ubiquitin-like protein ligase binding enzyme binding ligase activity protein domain specific binding ubiquitin binding ubiquitin-like protein binding NEDD8 transferase activity NEDD8 ligase activity ubiquitin-like protein ligase activity ubiquitin-protein transferase activity signaling receptor binding peroxisome proliferator activated receptor binding ubiquitin protein ligase activity identical protein binding p53 binding RNA binding organic cyclic compound binding rRNA binding 5S rRNA binding nucleic acid binding ribonucleoprotein complex binding protein-containing complex binding receptor serine/threonine kinase binding cation binding transition metal ion binding zinc ion binding ion binding metal ion binding small molecule binding disordered domain specific binding	response to stimulus response to chemical response to xenobiotic stimulus response to oxygen-containing compound response to formaldehyde regulation of biological process catabolic process regulation of protein metabolic process biological regulation primary metabolic process regulation of macromolecule metabolic process protein catabolic process regulation of catabolic process macromolecule catabolic process response to stimulus response to chemical response to xenobiotic stimulus response to oxygen-containing compound response to formaldehyde regulation of biological process catabolic process regulation of protein metabolic process biological regulation primary metabolic process regulation of macromolecule metabolic process protein catabolic process regulation of catabolic process macromolecule catabolic process regulation of primary metabolic process metabolic process protein metabolic process macromolecule metabolic process regulation of metabolic process regulation of protein catabolic process cellular response to nitrogen compound cellular response to stimulus response to endogenous stimulus response to peptide hormone cellular response to peptide hormone stimulus response to nitrogen compound cellular response to oxygen-containing compound cellular response to endogenous stimulus cellular response to chemical stimulus response to hormone cellular process cellular response to hormone stimulus regulation of cellular process signaling negative regulation of signaling negative regulation of intracellular signal transduction negative regulation of biological process regulation of signal transduction regulation of programmed cell death regulation of intrinsic apoptotic signaling pathway intracellular signal transduction negative regulation of cell communication cell communication regulation of intracellular signal transduction negative regulation of apoptotic signaling pathway regulation of signal transduction by p53 class mediator negative regulation of cellular process signal transduction intrinsic apoptotic signaling pathway negative regulation of signal transduction by p53 class mediator regulation of signaling negative regulation of response to stimulus negative regulation of programmed cell death regulation of apoptotic process signal transduction by p53 class mediator cell death negative regulation of signal transduction apoptotic signaling pathway negative regulation of intrinsic apoptotic signaling pathway negative regulation of apoptotic process negative regulation of intrinsic apoptotic signaling pathway by p53 class mediator regulation of response to stimulus regulation of cell communication intrinsic apoptotic signaling pathway by p53 class mediator apoptotic process regulation of intrinsic apoptotic signaling pathway by p53 class mediator programmed cell death regulation of apoptotic signaling pathway response to antibiotic protein autoubiquitination protein ubiquitination macromolecule modification post-translational protein modification protein modification process protein modification by small protein conjugation protein modification by small protein conjugation or removal peptidyl-lysine modification protein sumoylation peptidyl-amino acid modification positive regulation of proteasomal protein catabolic process positive regulation of protein metabolic process proteolysis involved in protein catabolic process positive regulation of biological process proteasome-mediated ubiquitin-dependent protein catabolic process regulation of ubiquitin-dependent protein catabolic process positive regulation of metabolic process positive regulation of ubiquitin-dependent protein catabolic process regulation of proteolysis regulation of proteolysis involved in protein catabolic process modification-dependent macromolecule catabolic process proteolysis positive regulation of macromolecule metabolic process proteasomal protein catabolic process positive regulation of protein catabolic process positive regulation of proteolysis involved in protein catabolic process positive regulation of catabolic process regulation of proteasomal ubiquitin-dependent protein catabolic process modification-dependent protein catabolic process positive regulation of proteolysis regulation of proteasomal protein catabolic process positive regulation of proteasomal ubiquitin-dependent protein catabolic process ubiquitin-dependent protein catabolic process fibroblast activation multicellular organismal process cell activation response to toxic substance response to metal ion response to iron ion response to immobilization stress response to stress response to water-immersion restraint stress response to estrogen cellular response to estrogen stimulus developmental process multicellular organism development anatomical structure development vasculature development blood vessel development system development circulatory system development cellular biosynthetic process RNA metabolic process negative regulation of cellular metabolic process negative regulation of RNA biosynthetic process RNA biosynthetic process nucleobase-containing compound metabolic process DNA-templated transcription nucleic acid biosynthetic process regulation of RNA metabolic process transcription by RNA polymerase II negative regulation of nucleobase-containing compound metabolic process regulation of nucleobase-containing compound metabolic process regulation of RNA biosynthetic process negative regulation of macromolecule metabolic process regulation of biosynthetic process regulation of transcription by RNA polymerase II negative regulation of DNA-templated transcription negative regulation of transcription by RNA polymerase II cellular metabolic process negative regulation of metabolic process regulation of cellular metabolic process nucleobase-containing compound biosynthetic process gene expression macromolecule biosynthetic process nucleic acid metabolic process negative regulation of cellular biosynthetic process regulation of cellular biosynthetic process regulation of gene expression biosynthetic process negative regulation of biosynthetic process negative regulation of macromolecule biosynthetic process regulation of macromolecule biosynthetic process regulation of DNA-templated transcription negative regulation of RNA metabolic process response to ether cellular component organization cellular component biogenesis cellular component assembly protein-containing complex organization protein-containing complex assembly cellular component organization or biogenesis heart development animal organ development ventricular septum development cardiac septum development cardiac chamber development cardiac ventricle development protein localization localization establishment of protein localization cellular localization cellular macromolecule localization macromolecule localization establishment of localization regulation of developmental process cellular developmental process regulation of cell differentiation muscle cell differentiation positive regulation of muscle cell differentiation muscle structure development positive regulation of developmental process regulation of muscle cell differentiation positive regulation of cell differentiation cell differentiation positive regulation of cellular process supramolecular fiber organization amyloid fibril formation regulation of cellular response to stress DNA damage response, signal transduction by p53 class mediator cellular response to stress regulation of response to stress negative regulation of DNA damage response, signal transduction by p53 class mediator regulation of DNA damage response, signal transduction by p53 class mediator DNA damage response signal transduction in response to DNA damage cell population proliferation positive regulation of cell population proliferation regulation of cell population proliferation response to light stimulus cellular response to radiation response to UV cellular response to environmental stimulus cellular response to UV-C response to UV-C cellular response to light stimulus response to radiation response to abiotic stimulus cellular response to abiotic stimulus cellular response to UV cardiac atrium development atrial septum development cellular response to growth factor stimulus response to growth factor regulation of protein maturation negative regulation of proteolysis negative regulation of protein maturation protein maturation negative regulation of protein metabolic process negative regulation of gene expression regulation of protein processing protein processing negative regulation of protein processing positive regulation of cell cycle mitotic cell cycle regulation of mitotic cell cycle positive regulation of mitotic cell cycle cell cycle regulation of cell cycle heart process system process regulation of heart contraction regulation of system process circulatory system process regulation of blood circulation regulation of multicellular organismal process regulation of biological quality heart contraction blood circulation regulation of heart rate protein destabilization regulation of protein stability positive regulation of cellular metabolic process positive regulation of macromolecule biosynthetic process positive regulation of biosynthetic process positive regulation of gene expression positive regulation of cellular biosynthetic process response to decreased oxygen levels cellular response to oxygen levels cellular response to hypoxia cellular response to decreased oxygen levels response to hypoxia response to oxygen levels cellular response to alkaloid response to alkaloid response to nutrient levels response to vitamin B1 response to alcohol response to nutrient cellular response to organic cyclic compound response to vitamin cellular response to vitamin B1 cellular response to nutrient levels cellular response to alcohol cellular response to vitamin cellular response to nutrient response to organic cyclic compound regulation of cell cycle phase transition traversing start control point of mitotic cell cycle cell cycle phase transition regulation of cell cycle G1/S phase transition cell cycle G1/S phase transition positive regulation of mitotic cell cycle phase transition positive regulation of cell cycle process cell cycle process positive regulation of G1/S transition of mitotic cell cycle regulation of cell cycle process regulation of mitotic cell cycle phase transition positive regulation of cell cycle G1/S phase transition mitotic cell cycle process regulation of G1/S transition of mitotic cell cycle positive regulation of cell cycle phase transition G1/S transition of mitotic cell cycle mitotic cell cycle phase transition regulation of neuron projection development regulation of cellular component organization cell projection organization cell development neuron projection development neurogenesis neuron differentiation negative regulation of cell projection organization plasma membrane bounded cell projection organization negative regulation of cellular component organization regulation of cell projection organization nervous system development negative regulation of neuron projection development generation of neurons neuron development regulation of plasma membrane bounded cell projection organization cardiac chamber morphogenesis heart morphogenesis anatomical structure morphogenesis cardiac septum morphogenesis animal organ morphogenesis protein polyubiquitination response to lipid response to steroid hormone response to actinomycin D cellular response to actinomycin D cellular response to antibiotic cellular response to ionizing radiation response to ionizing radiation cellular response to gamma radiation response to gamma radiation regulation of vascular associated smooth muscle cell proliferation positive regulation of vascular associated smooth muscle cell proliferation regulation of smooth muscle cell proliferation smooth muscle cell proliferation positive regulation of smooth muscle cell proliferation muscle cell proliferation vascular associated smooth muscle cell proliferation regulation of vascular associated smooth muscle cell migration positive regulation of locomotion vascular associated smooth muscle cell migration regulation of cell motility regulation of smooth muscle cell migration positive regulation of smooth muscle cell migration positive regulation of cell migration smooth muscle cell migration muscle cell migration regulation of locomotion positive regulation of cell motility regulation of cell migration cell migration cell motility locomotion positive regulation of vascular associated smooth muscle cell migration cellular response to oxidative stress cellular response to chemical stress cellular response to hydrogen peroxide response to reactive oxygen species response to hydrogen peroxide response to oxidative stress cellular response to reactive oxygen species regulation of localization nitrogen compound transport regulation of protein localization nucleocytoplasmic transport transport positive regulation of nucleocytoplasmic transport nuclear transport positive regulation of establishment of protein localization positive regulation of protein transport establishment of localization in cell positive regulation of intracellular transport nuclear export regulation of protein export from nucleus regulation of intracellular transport regulation of transport regulation of establishment of protein localization intracellular transport regulation of nucleocytoplasmic transport regulation of protein transport protein export from nucleus positive regulation of protein export from nucleus positive regulation of transport protein transport regulation of cellular localization positive regulation of protein localization regulation of intracellular protein transport positive regulation of intracellular protein transport intracellular protein transport mesenchyme morphogenesis endocardial cushion morphogenesis mesenchyme development tissue development tissue morphogenesis endocardial cushion development blood vessel remodeling tissue remodeling negative regulation of cell cycle negative regulation of mitotic cell cycle mitotic DNA integrity checkpoint signaling mitotic DNA damage checkpoint signaling negative regulation of cell cycle phase transition negative regulation of G1/S transition of mitotic cell cycle mitotic G1/S transition checkpoint signaling DNA integrity checkpoint signaling DNA damage checkpoint signaling negative regulation of mitotic cell cycle phase transition negative regulation of cell cycle G1/S phase transition negative regulation of cell cycle process cell cycle checkpoint signaling mitotic cell cycle checkpoint signaling mitotic G1 DNA damage checkpoint signaling DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest response to cocaine protein localization to organelle protein localization to nucleus atrioventricular valve development heart valve development heart valve morphogenesis atrioventricular valve morphogenesis response to magnesium ion	intracellular anatomical structure cytoplasm cellular anatomical entity cytosol membrane-bounded organelle nucleus membrane-enclosed lumen intracellular membrane-bounded organelle nucleolus intracellular organelle lumen intracellular organelle organelle lumen organelle intracellular non-membrane-bounded organelle intracellular anatomical structure cytoplasm cellular anatomical entity cytosol membrane-bounded organelle nucleus membrane-enclosed lumen intracellular membrane-bounded organelle nucleolus intracellular organelle lumen intracellular organelle organelle lumen organelle intracellular non-membrane-bounded organelle nuclear lumen non-membrane-bounded organelle cell periphery plasma membrane membrane protein-containing complex intracellular vesicle cytoplasmic vesicle membrane bounding membrane of organelle cytoplasmic vesicle vesicle membrane endocytic vesicle membrane vesicle organelle membrane endocytic vesicle nucleoplasm transcription regulator complex transcription repressor complex

InterPro: Protein Family Classification InterPro Database Homepage

Chains	Accession	Name	Type
A, B, C	IPR003121	SWIB/MDM2 domain	Domain
A, B, C	IPR016495	p53 negative regulator Mdm2/Mdm4	Family
A, B, C	IPR013083	Zinc finger, RING/FYVE/PHD-type	Homologous Superfamily
A, B, C	IPR001876	Zinc finger, RanBP2-type	Domain
A, B, C	IPR036443	Zinc finger, RanBP2-type superfamily	Homologous Superfamily
A, B, C	IPR036885	SWIB/MDM2 domain superfamily	Homologous Superfamily
A, B, C	IPR044080	MDM2, modified RING finger, HC subclass	Domain
A, B, C	IPR001841	Zinc finger, RING-type	Domain
A, B, C	IPR028340	E3 ubiquitin-protein ligase Mdm2	Family

Pharos: Disease Associations Pharos Homepage Annotation

Chains	Drug Target	Associated Disease
A, B, C	Pharos: Q00987	melanoma cancer Li-Fraumeni syndrome prostate cancer HIV infectious disease non-small cell lung carcinoma breast carcinoma well-differentiated liposarcoma male infertility precancerous condition gastric carcinoma hematologic disease SAPHO syndrome lipoma Subfertility, Male melanoma cancer Li-Fraumeni syndrome prostate cancer HIV infectious disease non-small cell lung carcinoma breast carcinoma well-differentiated liposarcoma male infertility precancerous condition gastric carcinoma hematologic disease SAPHO syndrome lipoma Subfertility, Male lymphatic system disease acute lymphoblastic leukemia amyotrophic lateral sclerosis breast cancer cutaneous melanoma peripheral nervous system disease exocrine pancreatic carcinoma glioblastoma hepatocellular carcinoma sarcoma juvenile dermatomyositis lung cancer urinary bladder cancer acute myeloid leukemia malignant colon neoplasm atypical lipomatous tumor malignant pancreatic neoplasm myopathy connective tissue disease osteosarcoma Dedifferentiated liposarcoma peripheral neuropathy gastric cancer primitive neuroectodermal tumor glioma psoriasis subependymal giant cell astrocytoma lung disease acute promyelocytic leukemia malignant mesothelioma atypical teratoid rhabdoid tumor breast disease colorectal adenocarcinoma Crohn disease ovarian cancer Emery-Dreifuss muscular dystrophy

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.