2HD4

Crystal structure of proteinase K inhibited by a lactoferrin octapeptide Gly-Asp-Glu-Gln-Gly-Glu-Asn-Lys at 2.15 A resolution

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	d2hd4a_	Alpha and beta proteins (a/b)	Subtilisin-like	Subtilisin-like	Subtilases	automated matches	(Parengyodontium album ) [TaxId: 37998 ],	SCOPe (2.08)

Domain Annotation: SCOP2 Classification SCOP2 Database Homepage

Chains	Type	Family Name	Domain Identifier	Family Identifier	Provenance Source (Version)
A	SCOP2B Superfamily	Subtilisin-like	8043920	3000226	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	Peptidase_S8	e2hd4A1	A: a/b three-layered sandwiches	X: Subtilisin-like	H: Subtilisin-like (From Topology)	T: Subtilisin-like	F: Peptidase_S8	ECOD (1.6)

Domain Annotation: CATH CATH Database Homepage

Chain	Domain	Class	Architecture	Topology	Homology	Provenance Source (Version)
A	3.40.50.200	Alpha Beta	3-Layer(aba) Sandwich	Rossmann fold	Peptidase S8/S53 domain	CATH (4.3.0)

Protein Family Annotation Pfam Database Homepage

Chains	Accession	Name	Description	Comments	Source
A	PF00082	Subtilase family (Peptidase_S8)	Subtilase family	Subtilases are a family of serine proteases. They appear to have independently and convergently evolved an Asp/Ser/His catalytic triad, like that found in the trypsin serine proteases (see Pfam:PF00089). Structure is an alpha/beta fold containing a 7 ...	Subtilases are a family of serine proteases. They appear to have independently and convergently evolved an Asp/Ser/His catalytic triad, like that found in the trypsin serine proteases (see Pfam:PF00089). Structure is an alpha/beta fold containing a 7-stranded parallel beta sheet, order 2314567.	Domain

Gene Ontology: Gene Product Annotation Gene Ontology Database Homepage

Chains	Polymer	Molecular Function	Biological Process	Cellular Component
A	Proteinase K	peptidase activity catalytic activity, acting on a protein serine hydrolase activity serine-type peptidase activity hydrolase activity serine-type endopeptidase activity catalytic activity endopeptidase activity cation binding ion binding binding metal ion binding small molecule binding	proteolysis metabolic process cellular process primary metabolic process protein metabolic process macromolecule metabolic process	cellular anatomical structure extracellular region extracellular space
B	8-mer Peptide from Lactotransferrin	enzyme regulator activity molecular function inhibitor activity peptidase regulator activity molecular function regulator activity enzyme inhibitor activity cysteine-type endopeptidase inhibitor activity peptidase inhibitor activity endopeptidase regulator activity endopeptidase inhibitor activity peptidase activity catalytic activity, acting on a protein serine hydrolase activity serine-type peptidase activity hydrolase activity enzyme regulator activity molecular function inhibitor activity peptidase regulator activity molecular function regulator activity enzyme inhibitor activity cysteine-type endopeptidase inhibitor activity peptidase inhibitor activity endopeptidase regulator activity endopeptidase inhibitor activity peptidase activity catalytic activity, acting on a protein serine hydrolase activity serine-type peptidase activity hydrolase activity serine-type endopeptidase activity catalytic activity endopeptidase activity DNA binding binding nucleic acid binding cation binding transition metal ion binding iron ion binding ion binding metal ion binding small molecule binding protein serine/threonine kinase activator activity kinase activator activity enzyme activator activity molecular function activator activity protein kinase activator activity protein kinase regulator activity kinase regulator activity lipid binding lipopolysaccharide binding carbohydrate derivative binding membrane destabilizing activity heparin binding glycosaminoglycan binding sulfur compound binding	regulation of biological process negative regulation of viral process regulation of viral process viral process biological regulation negative regulation of biological process humoral immune response biological process involved in interspecies interaction between organisms response to stimulus response to other organism defense response immune response antibacterial humoral response defense response to symbiont regulation of biological process negative regulation of viral process regulation of viral process viral process biological regulation negative regulation of biological process humoral immune response biological process involved in interspecies interaction between organisms response to stimulus response to other organism defense response immune response antibacterial humoral response defense response to symbiont response to external stimulus antimicrobial humoral response response to biotic stimulus defense response to bacterium defense response to other organism response to stress immune system process response to bacterium response to external biotic stimulus negative regulation of ATP-dependent activity regulation of ATP-dependent activity regulation of molecular function negative regulation of molecular function cell population proliferation regulation of cellular process positive regulation of cell population proliferation positive regulation of biological process positive regulation of chondrocyte proliferation regulation of cell population proliferation cellular process positive regulation of cellular process chondrocyte proliferation positive regulation of osteoblast proliferation osteoblast proliferation regulation of osteoblast proliferation positive regulation of DNA-binding transcription factor activity positive regulation of NF-kappaB transcription factor activity RNA metabolic process regulation of primary metabolic process nucleobase-containing compound metabolic process RNA biosynthetic process positive regulation of molecular function nucleic acid biosynthetic process DNA-templated transcription regulation of RNA metabolic process regulation of nucleobase-containing compound metabolic process regulation of RNA biosynthetic process regulation of biosynthetic process primary metabolic process regulation of macromolecule metabolic process nucleobase-containing compound biosynthetic process gene expression macromolecule biosynthetic process nucleic acid metabolic process regulation of gene expression biosynthetic process regulation of DNA-binding transcription factor activity metabolic process regulation of macromolecule biosynthetic process regulation of DNA-templated transcription macromolecule metabolic process regulation of metabolic process multicellular organismal process ossification cellular response to stimulus regulation of lipopolysaccharide-mediated signaling pathway negative regulation of lipopolysaccharide-mediated signaling pathway regulation of response to biotic stimulus negative regulation of response to biotic stimulus regulation of response to external stimulus response to lipid negative regulation of signaling signaling cellular response to lipopolysaccharide regulation of signal transduction negative regulation of cell communication cell communication lipopolysaccharide-mediated signaling pathway cellular response to biotic stimulus negative regulation of cellular process signal transduction regulation of signaling cell surface receptor signaling pathway negative regulation of response to stimulus response to oxygen-containing compound cellular response to molecule of bacterial origin negative regulation of signal transduction response to lipopolysaccharide cellular response to oxygen-containing compound cellular response to chemical stimulus regulation of response to stimulus negative regulation of response to external stimulus response to chemical cellular response to lipid regulation of cell communication response to molecule of bacterial origin disruption of cell in another organism disruption of anatomical structure in another organism killing of cells of another organism cell killing regulation of protein modification process positive regulation of phosphorylation regulation of catalytic activity regulation of protein phosphorylation positive regulation of protein metabolic process regulation of transferase activity positive regulation of phosphate metabolic process positive regulation of protein serine/threonine kinase activity positive regulation of metabolic process positive regulation of protein modification process regulation of phosphate metabolic process phosphate-containing compound metabolic process positive regulation of macromolecule metabolic process protein metabolic process positive regulation of protein kinase activity phosphorus metabolic process protein modification process positive regulation of protein phosphorylation protein phosphorylation positive regulation of transferase activity positive regulation of phosphorus metabolic process phosphorylation regulation of protein metabolic process positive regulation of catalytic activity regulation of protein kinase activity positive regulation of kinase activity regulation of kinase activity macromolecule modification regulation of protein serine/threonine kinase activity regulation of phosphorylation regulation of phosphorus metabolic process defense response to Gram-negative bacterium modulation by host of viral process negative regulation by host of viral process modulation of process of another organism host-mediated perturbation of symbiont process developmental process animal organ development multicellular organism development anatomical structure morphogenesis skeletal system development anatomical structure development skeletal system morphogenesis animal organ morphogenesis bone morphogenesis bone development system development defense response to fungus antifungal humoral response response to fungus positive regulation of cell communication positive regulation of signal transduction positive regulation of canonical NF-kappaB signal transduction intracellular signal transduction positive regulation of response to stimulus regulation of intracellular signal transduction intracellular signaling cassette positive regulation of intracellular signal transduction canonical NF-kappaB signal transduction regulation of canonical NF-kappaB signal transduction positive regulation of signaling positive regulation of response to biotic stimulus immune response-regulating cell surface receptor signaling pathway pattern recognition receptor signaling pathway immune response-activating signaling pathway positive regulation of immune response regulation of immune system process positive regulation of immune system process cell surface toll-like receptor signaling pathway innate immune response-activating signaling pathway positive regulation of pattern recognition receptor signaling pathway immune response-activating cell surface receptor signaling pathway regulation of innate immune response regulation of toll-like receptor 4 signaling pathway positive regulation of toll-like receptor 4 signaling pathway regulation of pattern recognition receptor signaling pathway positive regulation of defense response activation of innate immune response regulation of immune response activation of immune response regulation of defense response innate immune response activating cell surface receptor signaling pathway positive regulation of response to external stimulus immune response-regulating signaling pathway regulation of response to stress innate immune response cell surface pattern recognition receptor signaling pathway positive regulation of innate immune response toll-like receptor 4 signaling pathway localization transport iron ion transport transition metal ion transport monoatomic ion transport monoatomic cation transport establishment of localization metal ion transport negative regulation of programmed cell death regulation of apoptotic process regulation of programmed cell death cell death negative regulation of apoptotic process apoptotic process programmed cell death cell aggregation biofilm formation biological process involved in intraspecies interaction between organisms regulation of single-species biofilm formation in or on host organism single-species biofilm formation in or on host organism single-species biofilm formation negative regulation of single-species biofilm formation in or on host organism adhesion of symbiont to host biological process involved in interaction with host aggregation of unicellular organisms biological process involved in symbiotic interaction negative regulation of single-species biofilm formation regulation of single-species biofilm formation regulation of biological process involved in symbiotic interaction regulation of leukocyte differentiation regulation of cell differentiation regulation of cell development cell differentiation negative regulation of hemopoiesis regulation of osteoclast development negative regulation of leukocyte differentiation regulation of myeloid leukocyte differentiation negative regulation of myeloid cell differentiation negative regulation of myeloid leukocyte differentiation osteoclast development negative regulation of multicellular organismal process leukocyte differentiation myeloid leukocyte differentiation cellular developmental process regulation of developmental process cell development regulation of osteoclast differentiation bone cell development osteoclast differentiation regulation of multicellular organismal process negative regulation of cell differentiation regulation of multicellular organismal development hemopoiesis regulation of myeloid cell differentiation negative regulation of developmental process negative regulation of osteoclast differentiation negative regulation of cell development negative regulation of osteoclast development myeloid cell differentiation negative regulation of immune system process myeloid cell development regulation of hemopoiesis regulation of tumor necrosis factor production tumor necrosis factor superfamily cytokine production tumor necrosis factor production regulation of tumor necrosis factor superfamily cytokine production cytokine production regulation of cytokine production bone maturation regulation of bone mineralization involved in bone maturation regulation of biomineral tissue development regulation of bone mineralization positive regulation of ossification positive regulation of developmental process positive regulation of biomineral tissue development positive regulation of bone mineralization involved in bone maturation biomineral tissue development ossification involved in bone maturation bone mineralization bone mineralization involved in bone maturation developmental maturation tissue development positive regulation of bone mineralization anatomical structure maturation positive regulation of multicellular organismal process animal organ maturation regulation of ossification innate immune response in mucosa mucosal immune response organ or tissue specific immune response regulation of osteoblast differentiation osteoblast differentiation positive regulation of osteoblast differentiation positive regulation of cell differentiation antimicrobial humoral immune response mediated by antimicrobial peptide negative regulation of viral genome replication viral life cycle regulation of viral life cycle viral genome replication regulation of viral genome replication proteolysis negative regulation of tumor necrosis factor (ligand) superfamily member 11 production tumor necrosis factor (ligand) superfamily member 11 production negative regulation of macromolecule metabolic process negative regulation of metabolic process negative regulation of cytokine production regulation of tumor necrosis factor (ligand) superfamily member 11 production negative regulation of gene expression negative regulation of biosynthetic process negative regulation of macromolecule biosynthetic process negative regulation of tumor necrosis factor superfamily cytokine production	extracellular exosome membrane-bounded organelle extracellular vesicle cellular anatomical structure extracellular organelle extracellular region organelle extracellular space vesicle extracellular membrane-bounded organelle intracellular anatomical structure intracellular vesicle intracellular membrane-bounded organelle endomembrane system extracellular exosome membrane-bounded organelle extracellular vesicle cellular anatomical structure extracellular organelle extracellular region organelle extracellular space vesicle extracellular membrane-bounded organelle intracellular anatomical structure intracellular vesicle intracellular membrane-bounded organelle endomembrane system intracellular organelle cytoplasmic vesicle secretory granule secretory vesicle cytoplasm endosome recycling endosome vesicle lumen membrane-enclosed lumen cytoplasmic vesicle lumen secretory granule lumen intracellular organelle lumen organelle lumen specific granule lumen specific granule cell surface cell periphery plasma membrane membrane protein-containing complex phagocytic vesicle lumen phagocytic vesicle endocytic vesicle lumen endocytic vesicle early endosome tertiary granule lumen tertiary granule nucleus

InterPro: Protein Family Classification InterPro Database Homepage

Chains	Accession	Name	Type
A	IPR023828	Peptidase S8, subtilisin, Ser-active site	Active Site
A	IPR010259	Peptidase S8 propeptide/proteinase inhibitor I9	Domain
A	IPR022398	Peptidase S8, subtilisin, His-active site	Active Site
A	IPR000209	Peptidase S8/S53 domain	Domain
A	IPR015500	Peptidase S8, subtilisin-related	Family
A	IPR036852	Peptidase S8/S53 domain superfamily	Homologous Superfamily
A	IPR023827	Peptidase S8, subtilisin, Asp-active site	Active Site
A	IPR050131	Subtilisin-like serine protease	Family
A	IPR034193	Proteinase K-like catalytic domain	Domain
A	IPR037045	Peptidase S8 propeptide/proteinase inhibitor I9 superfamily	Homologous Superfamily
B	IPR001156	Transferrin-like domain	Domain
B	IPR016357	Transferrin	Family
B	IPR018195	Transferrin family, iron binding site	Binding Site
B	IPR030684	Lactotransferrin	Family

Pharos: Disease Associations Pharos Homepage Annotation

Chains	Drug Target	Associated Disease
B	Pharos: P02788	ulcerative colitis endometriosis oral candidiasis hypertensive disorder Inflammation osteoporosis arthropathy vulvovaginal candidiasis perinatal necrotizing enterocolitis cancer liver cancer malignant colon neoplasm necrotizing enterocolitis gastric cancer gelatinous drop-like corneal dystrophy ulcerative colitis endometriosis oral candidiasis hypertensive disorder Inflammation osteoporosis arthropathy vulvovaginal candidiasis perinatal necrotizing enterocolitis cancer liver cancer malignant colon neoplasm necrotizing enterocolitis gastric cancer gelatinous drop-like corneal dystrophy pancreatic intraductal papillary-mucinous neoplasm pituitary cancer Alzheimer disease psoriasis astrocytic tumor sinusitis benign neoplasm liver neoplasm colonic neoplasm malignant ependymoma diarrheal disease MALT lymphoma drug-induced liver injury exocrine pancreatic carcinoma gastric carcinoma osteosarcoma glioblastoma pancreatic intraductal papillary-mucinous neoplasm with low grade dysplasia atopic eczema inflammatory bowel disease subependymal giant cell astrocytoma breast cancer interstitial cystitis tuberculosis lymphoplasmacytic lymphoma cystic fibrosis malignant glioma nasopharyngeal carcinoma non-small cell lung carcinoma pancreatic ductal adenocarcinoma hepatocellular carcinoma asthma hypotensive disorder rheumatoid arthritis benign colon neoplasm injury celiac disease chronic kidney disease malignant pancreatic neoplasm

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.