DB code: D00232
RLCP classification | 1.13.10900.462 : Hydrolysis | |
---|---|---|
CATH domain | 3.40.390.10 : Collagenase (Catalytic Domain) | Catalytic domain |
2.110.10.10 : Hemopexin | ||
E.C. | 3.4.24.7 | |
CSA | ||
M-CSA | ||
MACiE |
CATH domain | Related DB codes (homologues) |
---|---|
2.110.10.10 : Hemopexin | M00101 |
3.40.390.10 : Collagenase (Catalytic Domain) | S00394 S00395 S00397 S00398 S00399 D00236 M00101 |
Uniprot Enzyme Name | UniprotKB | Protein name | Synonyms | Contains | RefSeq | MEROPS | Pfam |
---|---|---|---|---|---|---|
P21692 |
Interstitial collagenase
|
EC
3.4.24.7
Matrix metalloproteinase-1 MMP-1 |
18 kDa interstitial collagenase
|
NP_001159701.1
(Protein)
NM_001166229.1 (DNA/RNA sequence) |
M10.001
(Metallo)
|
PF00045
(Hemopexin)
PF00413 (Peptidase_M10) PF01471 (PG_binding_1) [Graphical View] |
P03956 |
Interstitial collagenase
|
EC
3.4.24.7
Matrix metalloproteinase-1 MMP-1 Fibroblast collagenase |
22 kDa interstitial collagenase
27 kDa interstitial collagenase |
NP_002412.1
(Protein)
NM_002421.3 (DNA/RNA sequence) |
M10.001
(Metallo)
|
PF00045
(Hemopexin)
PF00413 (Peptidase_M10) PF01471 (PG_binding_1) [Graphical View] |
KEGG enzyme name |
---|
interstitial collagenase
vertebrate collagenase matrix metalloproteinase 1 |
UniprotKB: Accession Number | Entry name | Activity | Subunit | Subcellular location | Cofactor |
---|---|---|---|---|---|
P21692 | MMP1_PIG | Cleavage of the triple helix of collagen at about three-quarters of the length of the molecule from the N- terminus, at 775-Gly-|-Ile-776 in the alpha-1(I) chain. Cleaves synthetic substrates and alpha-macroglobulins at bonds where P1'' is a hydrophobic residue. | Secreted, extracellular space, extracellular matrix (By similarity). | Binds 4 calcium ions per subunit. Binds 2 zinc ions per subunit. | |
P03956 | MMP1_HUMAN | Cleavage of the triple helix of collagen at about three-quarters of the length of the molecule from the N- terminus, at 775-Gly-|-Ile-776 in the alpha-1(I) chain. Cleaves synthetic substrates and alpha-macroglobulins at bonds where P1'' is a hydrophobic residue. | Interacts with HIV-1 Tat. | Secreted, extracellular space, extracellular matrix (Probable). | Binds 4 calcium ions per subunit. Binds 2 zinc ions per subunit. |
KEGG Pathways | Map code | Pathways | E.C. |
---|
Compound table | |||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Cofactors | Substrates | Products | Intermediates | ||||||||||
KEGG-id | C00038 | C00076 | C00211 | C00001 | C02898 | C00017 | C00012 | ||||||
E.C. | |||||||||||||
Compound | Zinc | Calcium | Collagen | H2O | alpha-Macroglobulin | Protein | Peptide | ||||||
Type | heavy metal | divalent metal (Ca2+, Mg2+) | amine group,carboxyl group,peptide/protein | H2O | peptide/protein | peptide/protein | peptide/protein | ||||||
ChEBI |
29105 29105 |
29108 29108 |
15377 15377 |
||||||||||
PubChem |
32051 32051 |
271 271 |
22247451 962 22247451 962 |
||||||||||
1fblA01 | Bound:2x_ZN | Bound:3x_CA | Unbound | Unbound | Unbound | Unbound | Intermediate-analogue:HTA | ||||||
1aykA | Bound:2x_ZN | Bound:_CA | Unbound | Unbound | Unbound | Unbound | Unbound | ||||||
1cgeA | Bound:2x_ZN | Bound:3x_CA | Unbound | Unbound | Unbound | Unbound | Unbound | ||||||
1cgfA | Bound:2x_ZN | Bound:3x_CA | Unbound | Unbound | Unbound | Unbound | Unbound | ||||||
1cgfB | Bound:2x_ZN | Bound:3x_CA | Unbound | Unbound | Unbound | Unbound | Unbound | ||||||
1cglA | Bound:2x_ZN | Bound:_CA | Unbound | Unbound | Unbound | Unbound | Intermediate-analogue:PHQ-ABU-LEU-PHE-EMR(chain C) | ||||||
1cglB | Bound:2x_ZN | Bound:_CA | Unbound | Unbound | Unbound | Unbound | Intermediate-analogue:PHQ-ABU-LEU-PHE-EMR(chain D) | ||||||
1hfcA | Bound:2x_ZN | Bound:_CA | Unbound | Unbound | Unbound | Unbound | Intermediate-analogue:PLH | ||||||
1su3A01 | Bound:2x_ZN | Bound:3x_CA | Unbound | Unbound | Unbound | Unbound | Unbound | ||||||
1su3B01 | Bound:2x_ZN | Bound:3x_CA | Unbound | Unbound | Unbound | Unbound | Unbound | ||||||
2aykA | Bound:2x_ZN | Bound:_CA | Unbound | Unbound | Unbound | Unbound | Unbound | ||||||
2tclA | Bound:2x_ZN | Bound:2x_CA | Unbound | Unbound | Unbound | Unbound | Intermediate-analogue:RO4 | ||||||
3aykA | Bound:2x_ZN | Bound:_CA | Unbound | Unbound | Unbound | Unbound | Intermediate-analogue:CGS | ||||||
4aykA | Bound:2x_ZN | Bound:_CA | Unbound | Unbound | Unbound | Unbound | Intermediate-analogue:CGS | ||||||
966cA | Bound:2x_ZN | Bound:3x_CA | Unbound | Unbound | Unbound | Unbound | Intermediate-analogue:RS2 | ||||||
1fblA02 | Unbound | Bound:_CA | Unbound | Unbound | Unbound | Unbound | Unbound | ||||||
1su3A02 | Unbound | Bound:_CA | Unbound | Unbound | Unbound | Unbound | Unbound | ||||||
1su3B02 | Unbound | Bound:_CA | Unbound | Unbound | Unbound | Unbound | Unbound |
Reference for Active-site residues | ||
---|---|---|
resource | references | E.C. |
Swiss-prot;P21692, P03956 |
Active-site residues | ||||||||||
---|---|---|---|---|---|---|---|---|---|---|
PDB | Catalytic residues | Cofactor-binding residues | Modified residues | Main-chain involved in catalysis | Comment | |||||
1fblA01 | ASN 180;GLU 219 | HIS 168;ASP 170;HIS 183;HIS 196(Non-catalytic zinc);HIS 218;HIS 222;HIS 228(Catalytic zinc) | ALA 182 | |||||||
1aykA | ASN 80;GLU 119 | HIS 68;ASP 70;HIS 83;HIS 96(Non-catalytic zinc);HIS 118;HIS 122;HIS 128(Catalytic zinc) | ALA 82 | |||||||
1cgeA | ASN 180;GLU 219 | HIS 168;ASP 170;HIS 183;HIS 196(Non-catalytic zinc);HIS 218;HIS 222;HIS 228(Catalytic zinc) | ALA 182 | |||||||
1cgfA | ASN 180;GLU 219 | HIS 168;ASP 170;HIS 183;HIS 196(Non-catalytic zinc);HIS 218;HIS 222;HIS 228(Catalytic zinc) | ALA 182 | |||||||
1cgfB | ASN 180;GLU 219 | HIS 168;ASP 170;HIS 183;HIS 196(Non-catalytic zinc);HIS 218;HIS 222;HIS 228(Catalytic zinc) | ALA 182 | |||||||
1cglA | ASN 180;GLU 219 | HIS 168;ASP 170;HIS 183;HIS 196(Non-catalytic zinc);HIS 218;HIS 222;HIS 228(Catalytic zinc) | ALA 182 | |||||||
1cglB | ASN 180;GLU 219 | HIS 168;ASP 170;HIS 183;HIS 196(Non-catalytic zinc);HIS 218;HIS 222;HIS 228(Catalytic zinc) | ALA 182 | |||||||
1hfcA | ASN 180;GLU 219 | HIS 168;ASP 170;HIS 183;HIS 196(Non-catalytic zinc);HIS 218;HIS 222;HIS 228(Catalytic zinc) | ALA 182 | |||||||
1su3A01 | ASN 180;GLU 219 | HIS 168;ASP 170;HIS 183;HIS 196(Non-catalytic zinc);HIS 218;HIS 222;HIS 228(Catalytic zinc) | ALA 182 | |||||||
1su3B01 | ASN 180;GLU 219 | HIS 168;ASP 170;HIS 183;HIS 196(Non-catalytic zinc);HIS 218;HIS 222;HIS 228(Catalytic zinc) | ALA 182 | |||||||
2aykA | ASN 80;GLU 119 | HIS 68;ASP 70;HIS 83;HIS 96(Non-catalytic zinc);HIS 118;HIS 122;HIS 128(Catalytic zinc) | ALA 82 | |||||||
2tclA | ASN 80;GLU 119 | HIS 68;ASP 70;HIS 83;HIS 96(Non-catalytic zinc);HIS 118;HIS 122;HIS 128(Catalytic zinc) | ALA 82 | |||||||
3aykA | ASN 80;GLU 119 | HIS 68;ASP 70;HIS 83;HIS 96(Non-catalytic zinc);HIS 118;HIS 122;HIS 128(Catalytic zinc) | ALA 82 | |||||||
4aykA | ASN 80;GLU 119 | HIS 68;ASP 70;HIS 83;HIS 96(Non-catalytic zinc);HIS 118;HIS 122;HIS 128(Catalytic zinc) | ALA 82 | |||||||
966cA | ASN 180;GLU 219 | HIS 168;ASP 170;HIS 183;HIS 196(Non-catalytic zinc);HIS 218;HIS 222;HIS 228(Catalytic zinc) | ALA 182 | |||||||
1fblA02 | ||||||||||
1su3A02 | ||||||||||
1su3B02 |
References for Catalytic Mechanism | ||
---|---|---|
References | Sections | No. of steps in catalysis |
[6]
|
Fig.5, p.8213-8214 | |
[8]
|
Fig.11, p.107-108 | |
[9]
|
p.376 |
References | |
---|---|
[1] | |
Resource | |
Comments | |
Medline ID | |
PubMed ID | 2153297 |
Journal | Proc Natl Acad Sci U S A |
Year | 1990 |
Volume | 87 |
Pages | 364-8 |
Authors | Springman EB, Angleton EL, Birkedal-Hansen H, Van Wart HE |
Title | Multiple modes of activation of latent human fibroblast collagenase: evidence for the role of a Cys73 active-site zinc complex in latency and a "cysteine switch" mechanism for activation. |
Related PDB | |
Related UniProtKB | |
[2] | |
Resource | |
Comments | |
Medline ID | |
PubMed ID | 1480035 |
Journal | Matrix Suppl |
Year | 1992 |
Volume | 1 |
Pages | 259-62 |
Authors | Galardy RE, Grobelny D, Kortylewicz ZP, Poncz L |
Title | Inhibition of human skin fibroblast collagenase by phosphorus-containing peptides. |
Related PDB | |
Related UniProtKB | |
[3] | |
Resource | |
Comments | |
Medline ID | |
PubMed ID | 1313176 |
Journal | Proteins |
Year | 1992 |
Volume | 12 |
Pages | 42-8 |
Authors | Lowry CL, McGeehan G, LeVine H 3rd |
Title | Metal ion stabilization of the conformation of a recombinant 19-kDa catalytic fragment of human fibroblast collagenase. |
Related PDB | |
Related UniProtKB | |
[4] | |
Resource | |
Comments | |
Medline ID | |
PubMed ID | 7978813 |
Journal | Ann N Y Acad Sci |
Year | 1994 |
Volume | 732 |
Pages | 375-8 |
Authors | Lovejoy B, Cleasby A, Hassell AM, Luther MA, Weigl D, McGeehan G, Lambert MH, Jordan SR |
Title | Structural analysis of the catalytic domain of human fibroblast collagenase. |
Related PDB | |
Related UniProtKB | |
[5] | |
Resource | |
Comments | |
Medline ID | |
PubMed ID | 7944383 |
Journal | Arch Biochem Biophys |
Year | 1994 |
Volume | 314 |
Pages | 120-5 |
Authors | Brownell J, Earley W, Kunec E, Morgan BA, Olyslager B, Wahl RC, Houck DR |
Title | Comparison of native matrix metalloproteinases and their recombinant catalytic domains using a novel radiometric assay. |
Related PDB | |
Related UniProtKB | |
[6] | |
Resource | |
Comments | X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 102-269. |
Medline ID | |
PubMed ID | 8031754 |
Journal | Biochemistry |
Year | 1994 |
Volume | 33 |
Pages | 8207-17 |
Authors | Lovejoy B, Hassell AM, Luther MA, Weigl D, Jordan SR |
Title | Crystal structures of recombinant 19-kDa human fibroblast collagenase complexed to itself. |
Related PDB | 1cge 1cgf |
Related UniProtKB | P03956 |
[7] | |
Resource | |
Comments | X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 100-269. |
Medline ID | 95384760 |
PubMed ID | 7656013 |
Journal | Nat Struct Biol |
Year | 1994 |
Volume | 1 |
Pages | 106-10 |
Authors | Borkakoti N, Winkler FK, Williams DH, D'Arcy A, Broadhurst MJ, Brown PA, Johnson WH, Murray EJ |
Title | Structure of the catalytic domain of human fibroblast collagenase complexed with an inhibitor. |
Related PDB | 2tcl |
Related UniProtKB | P03956 |
[8] | |
Resource | |
Comments | X-RAY CRYSTALLOGRAPHY (1.56 ANGSTROMS) OF 101-269. |
Medline ID | |
PubMed ID | 8090713 |
Journal | Proteins |
Year | 1994 |
Volume | 19 |
Pages | 98-109 |
Authors | Spurlino JC, Smallwood AM, Carlton DD, Banks TM, Vavra KJ, Johnson JS, Cook ER, Falvo J, Wahl RC, Pulvino TA, et al |
Title | 1.56 A structure of mature truncated human fibroblast collagenase. |
Related PDB | 1hfc |
Related UniProtKB | P03956 |
[9] | |
Resource | |
Comments | X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 102-269. |
Medline ID | 94105765 |
PubMed ID | 8278810 |
Journal | Science |
Year | 1994 |
Volume | 263 |
Pages | 375-7 |
Authors | Lovejoy B, Cleasby A, Hassell AM, Longley K, Luther MA, Weigl D, McGeehan G, McElroy AB, Drewry D, Lambert MH, et al |
Title | Structure of the catalytic domain of fibroblast collagenase complexed with an inhibitor. |
Related PDB | 1cgl |
Related UniProtKB | P03956 |
[10] | |
Resource | |
Comments | X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 100-469 |
Medline ID | 96173003 |
PubMed ID | 8590015 |
Journal | Structure |
Year | 1995 |
Volume | 3 |
Pages | 541-9 |
Authors | Li J, Brick P, O'Hare MC, Skarzynski T, Lloyd LF, Curry VA, Clark IM, Bigg HF, Hazleman BL, Cawston TE, et al |
Title |
Structure of full-length porcine synovial collagenase reveals a C-terminal domain containing a calcium-linked, |
Related PDB | 1fbl |
Related UniProtKB | P21692 |
[11] | |
Resource | |
Comments | |
Medline ID | |
PubMed ID | 9063449 |
Journal | Eur J Biochem |
Year | 1997 |
Volume | 244 |
Pages | 81-8 |
Authors | Vallon R, Muller R, Moosmayer D, Gerlach E, Angel P |
Title |
The catalytic domain of activated collagenase I (MMP-1) is absolutely required for interaction with its specific inhibitor, |
Related PDB | |
Related UniProtKB | |
[12] | |
Resource | |
Comments | |
Medline ID | |
PubMed ID | 9335112 |
Journal | J Biomol NMR |
Year | 1997 |
Volume | 10 |
Pages | 9-19 |
Authors | Moy FJ, Pisano MR, Chanda PK, Urbano C, Killar LM, Sung ML, Powers R |
Title |
Assignments, |
Related PDB | |
Related UniProtKB | |
[13] | |
Resource | |
Comments | STRUCTURE BY NMR OF 101-269. |
Medline ID | 98145213 |
PubMed ID | 9484219 |
Journal | Biochemistry |
Year | 1998 |
Volume | 37 |
Pages | 1495-504 |
Authors | Moy FJ, Chanda PK, Cosmi S, Pisano MR, Urbano C, Wilhelm J, Powers R |
Title | High-resolution solution structure of the inhibitor-free catalytic fragment of human fibroblast collagenase determined by multidimensional NMR. |
Related PDB | 1ayk |
Related UniProtKB | P03956 |
[14] | |
Resource | |
Comments | |
Medline ID | |
PubMed ID | 9844107 |
Journal | J Bone Miner Res |
Year | 1998 |
Volume | 13 |
Pages | 1890-902 |
Authors | Kremer EA, Chen Y, Suzuki K, Nagase H, Gorski JP |
Title | Hydroxyapatite induces autolytic degradation and inactivation of matrix metalloproteinase-1 and -3. |
Related PDB | |
Related UniProtKB | |
[15] | |
Resource | |
Comments | |
Medline ID | |
PubMed ID | 10548534 |
Journal | Biochem J |
Year | 1999 |
Volume | 344 Pt 1 |
Pages | 61-8 |
Authors | Little CB, Flannery CR, Hughes CE, Mort JS, Roughley PJ, Dent C, Caterson B |
Title | Aggrecanase versus matrix metalloproteinases in the catabolism of the interglobular domain of aggrecan in vitro. |
Related PDB | |
Related UniProtKB | |
[16] | |
Resource | |
Comments | NMR Structure |
Medline ID | |
PubMed ID | 10353819 |
Journal | Biochemistry |
Year | 1999 |
Volume | 38 |
Pages | 7085-96 |
Authors | Moy FJ, Chanda PK, Chen JM, Cosmi S, Edris W, Skotnicki JS, Wilhelm J, Powers R |
Title | NMR solution structure of the catalytic fragment of human fibroblast collagenase complexed with a sulfonamide derivative of a hydroxamic acid compound. |
Related PDB | 3ayk 4ayk |
Related UniProtKB | |
[17] | |
Resource | |
Comments | |
Medline ID | |
PubMed ID | 10074939 |
Journal | Nat Struct Biol |
Year | 1999 |
Volume | 6 |
Pages | 217-21 |
Authors | Lovejoy B, Welch AR, Carr S, Luong C, Broka C, Hendricks RT, Campbell JA, Walker KA, Martin R, Van Wart H, Browner MF |
Title | Crystal structures of MMP-1 and -13 reveal the structural basis for selectivity of collagenase inhibitors. |
Related PDB | 966c |
Related UniProtKB | |
[18] | |
Resource | |
Comments | |
Medline ID | |
PubMed ID | 11082208 |
Journal | Eur J Biochem |
Year | 2000 |
Volume | 267 |
Pages | 6943-50 |
Authors | Saito M, Sato K, Kunisaki N, Kimura S |
Title | Characterization of a rainbow trout matrix metalloproteinase capable of degrading type I collagen. |
Related PDB | |
Related UniProtKB | |
[19] | |
Resource | |
Comments | |
Medline ID | |
PubMed ID | 10871619 |
Journal | J Biol Chem |
Year | 2000 |
Volume | 275 |
Pages | 29610-7 |
Authors | Chung L, Shimokawa K, Dinakarpandian D, Grams F, Fields GB, Nagase H |
Title | Identification of the (183)RWTNNFREY(191) region as a critical segment of matrix metalloproteinase 1 for the expression of collagenolytic activity. |
Related PDB | |
Related UniProtKB | |
[20] | |
Resource | |
Comments | |
Medline ID | |
PubMed ID | 10926524 |
Journal | J Mol Biol |
Year | 2000 |
Volume | 301 |
Pages | 513-24 |
Authors | Zhang X, Gonnella NC, Koehn J, Pathak N, Ganu V, Melton R, Parker D, Hu SI, Nam KY |
Title | Solution structure of the catalytic domain of human collagenase-3 (MMP-13) complexed to a potent non-peptidic sulfonamide inhibitor: binding comparison with stromelysin-1 and collagenase-1. |
Related PDB | |
Related UniProtKB | |
[21] | |
Resource | |
Comments | |
Medline ID | |
PubMed ID | 11677139 |
Journal | Bioorg Med Chem Lett |
Year | 2001 |
Volume | 11 |
Pages | 2975-8 |
Authors | Levin JI, Chen JM, Du MT, Nelson FC, Wehr T, DiJoseph JF, Killar LM, Skala S, Sung A, Sharr MA, Roth CE, Jin G, Cowling R, Di L, Sherman M, Xu ZB, March CJ, Mohler KM, Black RA, Skotnicki JS |
Title |
The discovery of anthranilic acid-based MMP inhibitors. |
Related PDB | |
Related UniProtKB | |
[22] | |
Resource | |
Comments | |
Medline ID | |
PubMed ID | 11113146 |
Journal | J Biol Chem |
Year | 2001 |
Volume | 276 |
Pages | 10253-62 |
Authors | Balbin M, Fueyo A, Knauper V, Lopez JM, Alvarez J, Sanchez LM, Quesada V, Bordallo J, Murphy G, Lopez-Otin C |
Title | Identification and enzymatic characterization of two diverging murine counterparts of human interstitial collagenase (MMP-1) expressed at sites of embryo implantation. |
Related PDB | |
Related UniProtKB | |
[23] | |
Resource | |
Comments | |
Medline ID | |
PubMed ID | 11593430 |
Journal | Oncogene |
Year | 2001 |
Volume | 20 |
Pages | 6215-24 |
Authors | Bosc DG, Goueli BS, Janknecht R |
Title | HER2/Neu-mediated activation of the ETS transcription factor ER81 and its target gene MMP-1. |
Related PDB | |
Related UniProtKB | |
[24] | |
Resource | |
Comments | |
Medline ID | |
PubMed ID | 12595271 |
Journal | J Mol Biol |
Year | 2003 |
Volume | 326 |
Pages | 1651-65 |
Authors | Kallblad P, Dean PM |
Title | Efficient conformational sampling of local side-chain flexibility. |
Related PDB | |
Related UniProtKB | |
[25] | |
Resource | |
Comments | |
Medline ID | |
PubMed ID | 15611040 |
Journal | J Biol Chem |
Year | 2005 |
Volume | 280 |
Pages | 9578-85 |
Authors | Jozic D, Bourenkov G, Lim NH, Visse R, Nagase H, Bode W, Maskos K |
Title | X-ray structure of human proMMP-1: new insights into procollagenase activation and collagen binding. |
Related PDB | 1su3 |
Related UniProtKB |
Comments |
---|
Although this enzyme binds four calcium ions and two zinc ions, According to the literature [6], According to the literature [6] & [9] suggested that the catalytic zinc ion of this enzyme, According to the literature [6], (1) Carbonyl oxygen of target bond and hydrolytic water molecule are bound to zinc ion, (2) The water molecule makes a nucleophilic attack on the carbonyl carbon to form a tetrahedral intermediate. (3) The intermediate is stabilized by Asn180 and mainchain carbonyl of Ala113, (4) Glu219 acts as a genral acid to protonate the leaving amine group. |
Created | Updated |
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2005-02-16 | 2009-02-26 |