5I43

Crystal structure of the catalytic domain of MMP-12 in complex with a selective sugar-conjugated triazole-linked carboxylate chelator water-soluble inhibitor (DC32).

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	d5i43a_	Alpha and beta proteins (a+b)	Zincin-like	Metalloproteases ('zincins'), catalytic domain	Matrix metalloproteases, catalytic domain	Macrophage elastase (MMP-12)	Human (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)
B	d5i43b_	Alpha and beta proteins (a+b)	Zincin-like	Metalloproteases ('zincins'), catalytic domain	Matrix metalloproteases, catalytic domain	Macrophage elastase (MMP-12)	Human (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)
D	d5i43d_	Alpha and beta proteins (a+b)	Zincin-like	Metalloproteases ('zincins'), catalytic domain	Matrix metalloproteases, catalytic domain	Macrophage elastase (MMP-12)	Human (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)
C	d5i43c_	Alpha and beta proteins (a+b)	Zincin-like	Metalloproteases ('zincins'), catalytic domain	Matrix metalloproteases, catalytic domain	Macrophage elastase (MMP-12)	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	Metalloproteases (zincins), catalytic domain	8042292	3001975	SCOP2B (2022-06-29)
B	SCOP2B Superfamily	Metalloproteases (zincins), catalytic domain	8042292	3001975	SCOP2B (2022-06-29)
D	SCOP2B Superfamily	Metalloproteases (zincins), catalytic domain	8042292	3001975	SCOP2B (2022-06-29)
C	SCOP2B Superfamily	Metalloproteases (zincins), catalytic domain	8042292	3001975	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_M10	e5i43A1	A: mixed a+b and a/b	X: Zincin-like	H: Metalloproteases (zincins) catalytic domain (From Topology)	T: Metalloproteases (zincins) catalytic domain	F: Peptidase_M10	ECOD (1.6)
B	Peptidase_M10	e5i43B1	A: mixed a+b and a/b	X: Zincin-like	H: Metalloproteases (zincins) catalytic domain (From Topology)	T: Metalloproteases (zincins) catalytic domain	F: Peptidase_M10	ECOD (1.6)
D	Peptidase_M10	e5i43D1	A: mixed a+b and a/b	X: Zincin-like	H: Metalloproteases (zincins) catalytic domain (From Topology)	T: Metalloproteases (zincins) catalytic domain	F: Peptidase_M10	ECOD (1.6)
C	Peptidase_M10	e5i43C1	A: mixed a+b and a/b	X: Zincin-like	H: Metalloproteases (zincins) catalytic domain (From Topology)	T: Metalloproteases (zincins) catalytic domain	F: Peptidase_M10	ECOD (1.6)

Domain Annotation: CATH CATH Database Homepage

Chain	Domain	Class	Architecture	Topology	Homology	Provenance Source (Version)
A	3.40.390.10	Alpha Beta	3-Layer(aba) Sandwich	Collagenase (Catalytic Domain)	Collagenase (Catalytic Domain)	CATH (4.3.0)
B	3.40.390.10	Alpha Beta	3-Layer(aba) Sandwich	Collagenase (Catalytic Domain)	Collagenase (Catalytic Domain)	CATH (4.3.0)
D	3.40.390.10	Alpha Beta	3-Layer(aba) Sandwich	Collagenase (Catalytic Domain)	Collagenase (Catalytic Domain)	CATH (4.3.0)
C	3.40.390.10	Alpha Beta	3-Layer(aba) Sandwich	Collagenase (Catalytic Domain)	Collagenase (Catalytic Domain)	CATH (4.3.0)

Protein Family Annotation Pfam Database Homepage

Chains	Accession	Name	Description	Comments	Source
A, B, C, D	PF00413	Matrixin (Peptidase_M10)	Matrixin	The members of this family are enzymes that cleave peptides. These proteases require zinc for catalysis.	Domain

Gene Ontology: Gene Product Annotation Gene Ontology Database Homepage

Chains	Polymer	Molecular Function	Biological Process	Cellular Component
A, B, C, D	Macrophage metalloelastase	cation binding ion binding binding calcium ion binding metal ion binding small molecule binding peptidase activity catalytic activity, acting on a protein metalloendopeptidase activity hydrolase activity metallopeptidase activity catalytic activity endopeptidase activity DNA binding cation binding ion binding binding calcium ion binding metal ion binding small molecule binding peptidase activity catalytic activity, acting on a protein metalloendopeptidase activity hydrolase activity metallopeptidase activity catalytic activity endopeptidase activity DNA binding sequence-specific DNA binding sequence-specific double-stranded DNA binding transcription cis-regulatory region binding double-stranded DNA binding organic cyclic compound binding core promoter sequence-specific DNA binding nucleic acid binding transcription regulatory region nucleic acid binding serine hydrolase activity serine-type peptidase activity serine-type endopeptidase activity collagen binding protein-containing complex binding transition metal ion binding zinc ion binding	regulation of defense response regulation of response to biotic stimulus regulation of biological process biological process involved in interspecies interaction between organisms response to stimulus regulation of response to external stimulus response to other organism defense response biological regulation defense response to symbiont response to external stimulus response to biotic stimulus regulation of defense response to virus defense response to virus regulation of response to stimulus regulation of defense response regulation of response to biotic stimulus regulation of biological process biological process involved in interspecies interaction between organisms response to stimulus regulation of response to external stimulus response to other organism defense response biological regulation defense response to symbiont response to external stimulus response to biotic stimulus regulation of defense response to virus defense response to virus regulation of response to stimulus defense response to other organism response to stress regulation of response to stress regulation of defense response to virus by host response to external biotic stimulus response to virus collagen catabolic process catabolic process metabolic process cellular process collagen metabolic process wound healing cell population proliferation regulation of cellular process positive regulation of cell population proliferation positive regulation of epithelial cell proliferation positive regulation of biological process regulation of cell population proliferation regulation of epithelial cell proliferation response to wounding epithelial cell proliferation positive regulation of cellular process positive regulation of epithelial cell proliferation involved in wound healing endothelial cell-matrix adhesion negative regulation of endothelial cell-matrix adhesion via fibronectin regulation of cell-substrate adhesion regulation of cell adhesion negative regulation of biological process cell-substrate adhesion negative regulation of cell-matrix adhesion negative regulation of cell adhesion cell adhesion regulation of endothelial cell-matrix adhesion via fibronectin cell-matrix adhesion regulation of cell-matrix adhesion negative regulation of cellular process negative regulation of cell-substrate adhesion endothelial cell-matrix adhesion via fibronectin cellular response to stimulus regulation of type I interferon-mediated signaling pathway response to cytokine regulation of signal transduction cell communication interferon-mediated signaling pathway cellular response to type I interferon cellular response to cytokine stimulus regulation of immune system process signal transduction immune response regulation of innate immune response negative regulation of immune response regulation of response to cytokine stimulus negative regulation of response to cytokine stimulus response to chemical negative regulation of response to external stimulus negative regulation of defense response regulation of immune response response to type I interferon negative regulation of response to biotic stimulus negative regulation of signaling signaling negative regulation of cell communication cytokine-mediated signaling pathway innate immune response regulation of signaling cell surface receptor signaling pathway negative regulation of response to stimulus regulation of cytokine-mediated signaling pathway negative regulation of signal transduction response to peptide negative regulation of immune system process negative regulation of cytokine-mediated signaling pathway immune system process type I interferon-mediated signaling pathway regulation of cell communication negative regulation of type I interferon-mediated signaling pathway negative regulation of innate immune response cellular component organization extracellular matrix organization cellular component organization or biogenesis extracellular structure organization external encapsulating structure organization protein localization establishment of protein localization cellular localization nitrogen compound transport nucleocytoplasmic transport transport nuclear transport intracellular transport protein localization to nucleus establishment of localization localization import into nucleus establishment of protein localization to organelle protein transport cellular macromolecule localization macromolecule localization protein localization to organelle establishment of localization in cell protein import into nucleus intracellular protein transport cellular component disassembly extracellular matrix disassembly positive regulation of cell communication positive regulation of response to biotic stimulus positive regulation of signal transduction positive regulation of immune response positive regulation of immune system process positive regulation of defense response positive regulation of type I interferon-mediated signaling pathway positive regulation of response to cytokine stimulus positive regulation of response to stimulus positive regulation of response to external stimulus positive regulation of innate immune response positive regulation of cytokine-mediated signaling pathway positive regulation of signaling response to oxygen-containing compound response to nitrogen compound response to amyloid-beta developmental process epithelium development morphogenesis of an epithelium epiboly involved in wound healing tissue development morphogenesis of an epithelial sheet wound healing, spreading of epidermal cells tissue morphogenesis anatomical structure morphogenesis anatomical structure development epiboly cell migration wound healing, spreading of cells cell motility carbohydrate derivative catabolic process glycoprotein catabolic process elastin catabolic process carbohydrate derivative metabolic process primary metabolic process protein catabolic process glycoprotein metabolic process macromolecule catabolic process elastin metabolic process protein metabolic process macromolecule metabolic process RNA metabolic process regulation of primary 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 negative regulation of 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 negative regulation of biosynthetic process negative regulation of macromolecule biosynthetic process regulation of macromolecule biosynthetic process regulation of DNA-templated transcription regulation of metabolic process negative regulation of RNA metabolic process proteolysis positive regulation of DNA-templated transcription positive regulation of macromolecule biosynthetic process positive regulation of metabolic process positive regulation of biosynthetic process positive regulation of macromolecule metabolic process positive regulation of nucleobase-containing compound metabolic process positive regulation of transcription by RNA polymerase II positive regulation of RNA metabolic process positive regulation of RNA biosynthetic process multicellular organismal process interferon-alpha production cytokine production regulation of cytokine production regulation of multicellular organismal process regulation of interferon-alpha production positive regulation of type I interferon production type I interferon production positive regulation of interferon-alpha production positive regulation of gene expression positive regulation of multicellular organismal process positive regulation of cytokine production regulation of type I interferon production tube development respiratory tube development animal organ development bronchiole development multicellular organism development lung development respiratory system development system development lung alveolus development cellular response to virus	cellular anatomical structure intracellular anatomical structure cytoplasm cell periphery extracellular matrix external encapsulating structure extracellular region extracellular space membrane-bounded organelle intracellular organelle organelle nucleus intracellular membrane-bounded organelle

InterPro: Protein Family Classification InterPro Database Homepage

Chains	Accession	Name	Type
A, B, C, D	IPR018486	Hemopexin, conserved site	Conserved Site
A, B, C, D	IPR036375	Hemopexin-like domain superfamily	Homologous Superfamily
A, B, C, D	IPR021158	Peptidase M10A, cysteine switch, zinc binding site	Binding Site
A, B, C, D	IPR036365	PGBD-like superfamily	Homologous Superfamily
A, B, C, D	IPR001818	Peptidase M10, metallopeptidase	Domain
A, B, C, D	IPR021190	Peptidase M10A	Family
A, B, C, D	IPR002477	Peptidoglycan binding-like	Domain
A, B, C, D	IPR006026	Peptidase, metallopeptidase	Domain
A, B, C, D	IPR024079	Metallopeptidase, catalytic domain superfamily	Homologous Superfamily
A, B, C, D	IPR018487	Hemopexin-like repeats	Repeat
A, B, C, D	IPR000585	Hemopexin-like domain	Domain
A, B, C, D	IPR033739	Peptidase M10A, catalytic domain	Domain

Pharos: Disease Associations Pharos Homepage Annotation

Chains	Drug Target	Associated Disease
A, B, C, D	Pharos: P39900	rheumatoid arthritis Weight Gain malignant colon neoplasm pulmonary emphysema interstitial cystitis lung cancer malignant pancreatic neoplasm non-small cell lung carcinoma pancreatic intraductal papillary-mucinous neoplasm with low grade dysplasia Alzheimer disease psoriasis benign colon neoplasm sarcoidosis colonic neoplasm esophageal adenocarcinoma rheumatoid arthritis Weight Gain malignant colon neoplasm pulmonary emphysema interstitial cystitis lung cancer malignant pancreatic neoplasm non-small cell lung carcinoma pancreatic intraductal papillary-mucinous neoplasm with low grade dysplasia Alzheimer disease psoriasis benign colon neoplasm sarcoidosis colonic neoplasm esophageal adenocarcinoma head and neck cancer invasive ductal breast carcinoma medulloblastoma ovarian cancer periodontitis atopic eczema breast cancer cerebrovascular disorder Crohn disease IgA glomerulonephritis lung adenocarcinoma malignant glioma nasopharyngeal carcinoma peripheral arterial disease atypical teratoid rhabdoid tumor ulcerative colitis chronic obstructive pulmonary disease ductal breast carcinoma in situ glioblastoma

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.