1DVA

Crystal Structure of the Complex Between the Peptide Exosite Inhibitor E-76 and Coagulation Factor VIIA

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)
D [auth I]	d1dvai_	All beta proteins	Trypsin-like serine proteases	Trypsin-like serine proteases	Eukaryotic proteases	Coagulation factor VIIa	human (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)
A [auth H]	d1dvah_	All beta proteins	Trypsin-like serine proteases	Trypsin-like serine proteases	Eukaryotic proteases	Coagulation factor VIIa	human (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)
B [auth L]	d1dval1	Small proteins	Knottins (small inhibitors, toxins, lectins)	EGF/Laminin	EGF-type module	Coagulation factor VIIa	human (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)
E [auth M]	d1dvam1	Small proteins	Knottins (small inhibitors, toxins, lectins)	EGF/Laminin	EGF-type module	Coagulation factor VIIa	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)
D [auth I]	SCOP2B Superfamily	Trypsin-like serine proteases	8003776	3000114	SCOP2B (2022-06-29)
A [auth H]	SCOP2B Superfamily	Trypsin-like serine proteases	8003776	3000114	SCOP2B (2022-06-29)
B [auth L]	SCOP2B Superfamily	EGF/Laminin-like	8039292	3000412	SCOP2B (2022-06-29)
B [auth L]	SCOP2B Superfamily	EGF/Laminin-like	8039297	3000412	SCOP2B (2022-06-29)
E [auth M]	SCOP2B Superfamily	EGF/Laminin-like	8039292	3000412	SCOP2B (2022-06-29)
E [auth M]	SCOP2B Superfamily	EGF/Laminin-like	8039297	3000412	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)
D [auth I]	Trypsin_1	e1dvaI1	A: beta barrels	X: cradle loop barrel	H: RIFT-related	T: FMN-binding split barrel 2	F: Trypsin_1	ECOD (1.6)
A [auth H]	Trypsin_1	e1dvaH1	A: beta barrels	X: cradle loop barrel	H: RIFT-related	T: FMN-binding split barrel 2	F: Trypsin_1	ECOD (1.6)
B [auth L]	FXa_inhibition	e1dvaL2	A: few secondary structure elements	X: EGF-like	H: EGF-related	T: EGF/Laminin	F: FXa_inhibition	ECOD (1.6)
B [auth L]	hEGF_3	e1dvaL1	A: few secondary structure elements	X: EGF-like	H: EGF-related	T: EGF/Laminin	F: hEGF_3	ECOD (1.6)
E [auth M]	FXa_inhibition	e1dvaM2	A: few secondary structure elements	X: EGF-like	H: EGF-related	T: EGF/Laminin	F: FXa_inhibition	ECOD (1.6)
E [auth M]	hEGF_3	e1dvaM1	A: few secondary structure elements	X: EGF-like	H: EGF-related	T: EGF/Laminin	F: hEGF_3	ECOD (1.6)

Domain Annotation: CATH CATH Database Homepage

Chain	Domain	Class	Architecture	Topology	Homology	Provenance Source (Version)
D [auth I]	2.40.10.10	Mainly Beta	Beta Barrel	Thrombin, subunit H	Trypsin-like serine proteases	CATH (4.3.0)
A [auth H]	2.40.10.10	Mainly Beta	Beta Barrel	Thrombin, subunit H	Trypsin-like serine proteases	CATH (4.3.0)
B [auth L]	2.10.25.10	Mainly Beta	Ribbon	Laminin	Laminin	CATH (4.3.0)
E [auth M]	2.10.25.10	Mainly Beta	Ribbon	Laminin	Laminin	CATH (4.3.0)

Protein Family Annotation Pfam Database Homepage

Chains	Accession	Name	Description	Comments	Source
A [auth H], D [auth I]	PF00089	Trypsin (Trypsin)	Trypsin	-	Domain
B [auth L], E [auth M]	PF00008	EGF-like domain (EGF)	EGF-like domain	There is no clear separation between noise and signal. Pfam:PF00053 is very similar, but has 8 instead of 6 conserved cysteines. Includes some cytokine receptors. The EGF domain misses the N-terminus regions of the Ca2+ binding EGF domains (this is t ...	There is no clear separation between noise and signal. Pfam:PF00053 is very similar, but has 8 instead of 6 conserved cysteines. Includes some cytokine receptors. The EGF domain misses the N-terminus regions of the Ca2+ binding EGF domains (this is the main reason of discrepancy between swiss-prot domain start/end and Pfam). The family is hard to model due to many similar but different sub-types of EGF domains. Pfam certainly misses a number of EGF domains.	Domain
B [auth L], E [auth M]	PF14670	Coagulation Factor Xa inhibitory site (FXa_inhibition)	Coagulation Factor Xa inhibitory site	This short domain on coagulation enzyme factor Xa is found to be the target for a potent inhibitor of coagulation, TAK-442 [1].	Domain
B [auth L], E [auth M]	PF00594	Vitamin K-dependent carboxylation/gamma-carboxyglutamic (GLA) domain (Gla)	Vitamin K-dependent carboxylation/gamma-carboxyglutamic (GLA) domain	This domain is responsible for the high-affinity binding of calcium ions. This domain contains post-translational modifications of many glutamate residues by Vitamin K-dependent carboxylation to form gamma-carboxyglutamate (Gla).	Domain

Gene Ontology: Gene Product Annotation Gene Ontology Database Homepage

Chains	Polymer	Molecular Function	Biological Process	Cellular Component
A [auth H], D [auth I]	DES-GLA FACTOR VIIA (HEAVY CHAIN)	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 calcium ion binding metal ion binding small molecule binding 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 calcium ion binding metal ion binding small molecule binding protein binding signaling receptor binding	multicellular organismal process regulation of body fluid levels wound healing response to stimulus hemostasis biological regulation blood coagulation response to stress coagulation regulation of biological quality response to wounding response to organic substance response to lipid response to chemical multicellular organismal process regulation of body fluid levels wound healing response to stimulus hemostasis biological regulation blood coagulation response to stress coagulation regulation of biological quality response to wounding response to organic substance response to lipid response to chemical response to astaxanthin cellular response to stimulus positive regulation of cell communication regulation of cellular process positive regulation of signal transduction signaling positive regulation of biological process regulation of signal transduction intracellular signal transduction cell communication positive regulation of response to stimulus regulation of intracellular signal transduction positive regulation of TOR signaling signal transduction positive regulation of cellular process TOR signaling regulation of biological process regulation of signaling regulation of TOR signaling positive regulation of intracellular signal transduction regulation of response to stimulus regulation of cell communication cellular process positive regulation of signaling response to sterol response to alcohol response to oxygen-containing compound response to cholesterol response to organic cyclic compound response to thyrotropin-releasing hormone response to hormone response to endogenous stimulus response to organonitrogen compound response to peptide hormone response to nitrogen compound response to carbon dioxide response to thyroid hormone response to thyroxine response to amino acid response to L-phenylalanine derivative response to acid chemical response to growth hormone response to decreased oxygen levels response to hypoxia response to oxygen levels response to abiotic stimulus positive regulation of coagulation regulation of response to external stimulus positive regulation of blood coagulation regulation of response to wounding regulation of coagulation regulation of response to stress regulation of multicellular organismal process positive regulation of hemostasis regulation of hemostasis positive regulation of response to wounding regulation of blood coagulation response to external stimulus positive regulation of wound healing regulation of wound healing positive regulation of multicellular organismal process positive regulation of locomotion regulation of cell motility positive regulation of chemotaxis positive regulation of cell migration positive regulation of response to external stimulus taxis positive regulation of cell motility regulation of cell migration cell migration regulation of immune system process cell motility positive regulation of immune system process locomotion cell chemotaxis chemotaxis regulation of leukocyte chemotaxis regulation of leukocyte migration positive regulation of leukocyte chemotaxis positive regulation of leukocyte migration regulation of chemotaxis leukocyte migration cellular response to chemical stimulus immune system process regulation of locomotion leukocyte chemotaxis regulation of platelet-derived growth factor receptor signaling pathway cell surface receptor protein tyrosine kinase signaling pathway enzyme-linked receptor protein signaling pathway positive regulation of platelet-derived growth factor receptor signaling pathway cell surface receptor signaling pathway platelet-derived growth factor receptor signaling pathway rhythmic process circadian rhythm response to estrogen organonitrogen compound metabolic process cellular biosynthetic process cellular metabolic process primary metabolic process gene expression macromolecule biosynthetic process protein maturation organic substance metabolic process biosynthetic process proteolysis organic substance biosynthetic process protein processing metabolic process protein metabolic process macromolecule metabolic process response to Thyroid stimulating hormone response to glycoprotein response to 2,3,7,8-tetrachlorodibenzodioxine positive chemotaxis positive regulation of positive chemotaxis regulation of positive chemotaxis response to phenylpropanoid response to ketone response to hydroxyisoflavone response to genistein developmental process animal organ regeneration animal organ development anatomical structure development regeneration response to nutrient levels response to nutrient response to vitamin K response to vitamin response to estradiol	cell periphery extracellular matrix external encapsulating structure collagen-containing extracellular matrix cellular anatomical entity membrane-bounded organelle intracellular anatomical structure membrane-enclosed lumen intracellular membrane-bounded organelle endomembrane system intracellular organelle lumen endoplasmic reticulum lumen intracellular organelle organelle lumen cell periphery extracellular matrix external encapsulating structure collagen-containing extracellular matrix cellular anatomical entity membrane-bounded organelle intracellular anatomical structure membrane-enclosed lumen intracellular membrane-bounded organelle endomembrane system intracellular organelle lumen endoplasmic reticulum lumen intracellular organelle organelle lumen organelle endoplasmic reticulum cytoplasm extracellular region extracellular space vesicle plasma membrane membrane Golgi apparatus Golgi lumen protein-containing complex catalytic complex peptidase complex serine-type peptidase complex
B [auth L], E [auth M]	DES-GLA FACTOR VIIA (LIGHT CHAIN)	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 calcium ion binding metal ion binding small molecule binding 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 calcium ion binding metal ion binding small molecule binding protein binding signaling receptor binding	multicellular organismal process regulation of body fluid levels wound healing response to stimulus hemostasis biological regulation blood coagulation response to stress coagulation regulation of biological quality response to wounding response to organic substance response to lipid response to chemical multicellular organismal process regulation of body fluid levels wound healing response to stimulus hemostasis biological regulation blood coagulation response to stress coagulation regulation of biological quality response to wounding response to organic substance response to lipid response to chemical response to astaxanthin cellular response to stimulus positive regulation of cell communication regulation of cellular process positive regulation of signal transduction signaling positive regulation of biological process regulation of signal transduction intracellular signal transduction cell communication positive regulation of response to stimulus regulation of intracellular signal transduction positive regulation of TOR signaling signal transduction positive regulation of cellular process TOR signaling regulation of biological process regulation of signaling regulation of TOR signaling positive regulation of intracellular signal transduction regulation of response to stimulus regulation of cell communication cellular process positive regulation of signaling response to sterol response to alcohol response to oxygen-containing compound response to cholesterol response to organic cyclic compound response to thyrotropin-releasing hormone response to hormone response to endogenous stimulus response to organonitrogen compound response to peptide hormone response to nitrogen compound response to carbon dioxide response to thyroid hormone response to thyroxine response to amino acid response to L-phenylalanine derivative response to acid chemical response to growth hormone response to decreased oxygen levels response to hypoxia response to oxygen levels response to abiotic stimulus positive regulation of coagulation regulation of response to external stimulus positive regulation of blood coagulation regulation of response to wounding regulation of coagulation regulation of response to stress regulation of multicellular organismal process positive regulation of hemostasis regulation of hemostasis positive regulation of response to wounding regulation of blood coagulation response to external stimulus positive regulation of wound healing regulation of wound healing positive regulation of multicellular organismal process positive regulation of locomotion regulation of cell motility positive regulation of chemotaxis positive regulation of cell migration positive regulation of response to external stimulus taxis positive regulation of cell motility regulation of cell migration cell migration regulation of immune system process cell motility positive regulation of immune system process locomotion cell chemotaxis chemotaxis regulation of leukocyte chemotaxis regulation of leukocyte migration positive regulation of leukocyte chemotaxis positive regulation of leukocyte migration regulation of chemotaxis leukocyte migration cellular response to chemical stimulus immune system process regulation of locomotion leukocyte chemotaxis regulation of platelet-derived growth factor receptor signaling pathway cell surface receptor protein tyrosine kinase signaling pathway enzyme-linked receptor protein signaling pathway positive regulation of platelet-derived growth factor receptor signaling pathway cell surface receptor signaling pathway platelet-derived growth factor receptor signaling pathway rhythmic process circadian rhythm response to estrogen organonitrogen compound metabolic process cellular biosynthetic process cellular metabolic process primary metabolic process gene expression macromolecule biosynthetic process protein maturation organic substance metabolic process biosynthetic process proteolysis organic substance biosynthetic process protein processing metabolic process protein metabolic process macromolecule metabolic process response to Thyroid stimulating hormone response to glycoprotein response to 2,3,7,8-tetrachlorodibenzodioxine positive chemotaxis positive regulation of positive chemotaxis regulation of positive chemotaxis response to phenylpropanoid response to ketone response to hydroxyisoflavone response to genistein developmental process animal organ regeneration animal organ development anatomical structure development regeneration response to nutrient levels response to nutrient response to vitamin K response to vitamin response to estradiol	cell periphery extracellular matrix external encapsulating structure collagen-containing extracellular matrix cellular anatomical entity membrane-bounded organelle intracellular anatomical structure membrane-enclosed lumen intracellular membrane-bounded organelle endomembrane system intracellular organelle lumen endoplasmic reticulum lumen intracellular organelle organelle lumen cell periphery extracellular matrix external encapsulating structure collagen-containing extracellular matrix cellular anatomical entity membrane-bounded organelle intracellular anatomical structure membrane-enclosed lumen intracellular membrane-bounded organelle endomembrane system intracellular organelle lumen endoplasmic reticulum lumen intracellular organelle organelle lumen organelle endoplasmic reticulum cytoplasm extracellular region extracellular space vesicle plasma membrane membrane Golgi apparatus Golgi lumen protein-containing complex catalytic complex peptidase complex serine-type peptidase complex
C [auth X], F [auth Y]	PEPTIDE E-76	-	-	-

InterPro: Protein Family Classification InterPro Database Homepage

Chains	Accession	Name	Type
A [auth H], D [auth I]	IPR018097	EGF-like calcium-binding, conserved site	Conserved Site
A [auth H], D [auth I]	IPR018114	Serine proteases, trypsin family, histidine active site	Active Site
A [auth H], D [auth I]	IPR009003	Peptidase S1, PA clan	Homologous Superfamily
A [auth H], D [auth I]	IPR033116	Serine proteases, trypsin family, serine active site	Active Site
A [auth H], D [auth I]	IPR001254	Serine proteases, trypsin domain	Domain
A [auth H], D [auth I]	IPR035972	Gamma-carboxyglutamic acid-rich (GLA) domain superfamily	Homologous Superfamily
A [auth H], D [auth I]	IPR001881	EGF-like calcium-binding domain	Domain
A [auth H], D [auth I]	IPR012224	Peptidase S1A, coagulation factor VII/IX/X/C/Z	Family
A [auth H], D [auth I]	IPR000294	Gamma-carboxyglutamic acid-rich (GLA) domain	Domain
A [auth H], D [auth I]	IPR000742	EGF-like domain	Domain
A [auth H], D [auth I]	IPR017857	Coagulation factor-like, Gla domain superfamily	Homologous Superfamily
A [auth H], D [auth I]	IPR001314	Peptidase S1A, chymotrypsin family	Family
A [auth H], D [auth I]	IPR043504	Peptidase S1, PA clan, chymotrypsin-like fold	Homologous Superfamily
A [auth H], D [auth I]	IPR000152	EGF-type aspartate/asparagine hydroxylation site	PTM
B [auth L], E [auth M]	IPR018097	EGF-like calcium-binding, conserved site	Conserved Site
B [auth L], E [auth M]	IPR018114	Serine proteases, trypsin family, histidine active site	Active Site
B [auth L], E [auth M]	IPR009003	Peptidase S1, PA clan	Homologous Superfamily
B [auth L], E [auth M]	IPR033116	Serine proteases, trypsin family, serine active site	Active Site
B [auth L], E [auth M]	IPR001254	Serine proteases, trypsin domain	Domain
B [auth L], E [auth M]	IPR035972	Gamma-carboxyglutamic acid-rich (GLA) domain superfamily	Homologous Superfamily
B [auth L], E [auth M]	IPR001881	EGF-like calcium-binding domain	Domain
B [auth L], E [auth M]	IPR012224	Peptidase S1A, coagulation factor VII/IX/X/C/Z	Family
B [auth L], E [auth M]	IPR000294	Gamma-carboxyglutamic acid-rich (GLA) domain	Domain
B [auth L], E [auth M]	IPR000742	EGF-like domain	Domain
B [auth L], E [auth M]	IPR017857	Coagulation factor-like, Gla domain superfamily	Homologous Superfamily
B [auth L], E [auth M]	IPR001314	Peptidase S1A, chymotrypsin family	Family
B [auth L], E [auth M]	IPR043504	Peptidase S1, PA clan, chymotrypsin-like fold	Homologous Superfamily
B [auth L], E [auth M]	IPR000152	EGF-type aspartate/asparagine hydroxylation site	PTM

Pharos: Disease Associations Pharos Homepage Annotation

Chains	Drug Target	Associated Disease
A [auth H], D [auth I]	Pharos: P08709	congenital factor VII deficiency Venous Thrombosis disseminated intravascular coagulation factor VII deficiency myocardial infarction hemorrhagic disease malignant mesothelioma pancreatic ductal adenocarcinoma atrial fibrillation intracranial hemorrhage large cell medulloblastoma medulloblastoma thrombophilia atypical teratoid rhabdoid tumor glioblastoma congenital factor VII deficiency Venous Thrombosis disseminated intravascular coagulation factor VII deficiency myocardial infarction hemorrhagic disease malignant mesothelioma pancreatic ductal adenocarcinoma atrial fibrillation intracranial hemorrhage large cell medulloblastoma medulloblastoma thrombophilia atypical teratoid rhabdoid tumor glioblastoma intracerebral hemorrhage malignant glioma thrombotic disease congenital factor XI deficiency
B [auth L], E [auth M]	Pharos: P08709	congenital factor VII deficiency Venous Thrombosis disseminated intravascular coagulation factor VII deficiency myocardial infarction hemorrhagic disease malignant mesothelioma pancreatic ductal adenocarcinoma atrial fibrillation intracranial hemorrhage large cell medulloblastoma medulloblastoma thrombophilia atypical teratoid rhabdoid tumor glioblastoma congenital factor VII deficiency Venous Thrombosis disseminated intravascular coagulation factor VII deficiency myocardial infarction hemorrhagic disease malignant mesothelioma pancreatic ductal adenocarcinoma atrial fibrillation intracranial hemorrhage large cell medulloblastoma medulloblastoma thrombophilia atypical teratoid rhabdoid tumor glioblastoma intracerebral hemorrhage malignant glioma thrombotic disease congenital factor XI deficiency

Protein Modification Annotation

Modified Residue(s)
Chain	Residue(s)	Description
C [auth X], F [auth Y]	ACE	RESID: AA0041 , AA0042 , AA0043 , AA0044 , AA0045 , AA0046 , AA0049 , AA0050 , AA0051 , AA0052 , AA0053 , AA0054 , AA0354 PSI-MOD : N-acetyl-L-alanine MOD:00050 , N-acetyl-L-aspartic acid MOD:00051 , N-acetyl-L-cysteine MOD:00052 , N-acetyl-S-archeol-cysteine MOD:00897 , N-acetyl-L-glutamic acid MOD:00053 , N-acetyl-L-glutamine MOD:00054 , N-acetylglycine MOD:00055 , N-acetyl-L-methionine MOD:00058 , N-acetyl-L-proline MOD:00059 , N-acetyl-L-serine MOD:00060 , N,O-diacetylated L-serine MOD:00648 , N-acetyl-L-threonine MOD:00061 , N-acetyl-L-tyrosine MOD:00062 , N-acetyl-L-valine MOD:00063 , N2-acetyl-L-arginine MOD:00359
C [auth X], F [auth Y]	NH2	RESID: AA0041 , AA0042 , AA0043 , AA0044 , AA0045 , AA0046 , AA0049 , AA0050 , AA0051 , AA0052 , AA0053 , AA0054 , AA0354 , AA0081 , AA0083 , AA0084 , AA0086 , AA0087 , AA0088 , AA0090 , AA0091 , AA0092 , AA0093 , AA0095 , AA0096 , AA0097 , AA0098 , AA0099 , AA0100 PSI-MOD : N-acetyl-L-alanine MOD:00050 , N-acetyl-L-aspartic acid MOD:00051 , N-acetyl-L-cysteine MOD:00052 , N-acetyl-S-archeol-cysteine MOD:00897 , N-acetyl-L-glutamic acid MOD:00053 , N-acetyl-L-glutamine MOD:00054 , N-acetylglycine MOD:00055 , N-acetyl-L-methionine MOD:00058 , N-acetyl-L-proline MOD:00059 , N-acetyl-L-serine MOD:00060 , N,O-diacetylated L-serine MOD:00648 , N-acetyl-L-threonine MOD:00061 , N-acetyl-L-tyrosine MOD:00062 , N-acetyl-L-valine MOD:00063 , N2-acetyl-L-arginine MOD:00359 , L-alanine amide MOD:00090 , L-asparagine amide MOD:00092 , L-aspartic acid 1-amide MOD:00093 , L-glutamine amide MOD:00095 , L-glutamic acid 1-amide MOD:00096 , glycine amide MOD:00097 , L-isoleucine amide MOD:00099 , L-leucine amide MOD:00100 , L-lysine amide MOD:00101 , L-methionine amide MOD:00102 , L-proline amide MOD:00104 , L-serine amide MOD:00105 , L-threonine amide MOD:00106 , L-tryptophan amide MOD:00107 , L-tyrosine amide MOD:00108 , L-valine amide MOD:00109