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)
3.40.390.10 : Collagenase (Catalytic Domain) S00394 S00395 S00397 S00398 S00399 D00236 M00101
2.110.10.10 : Hemopexin 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
Fibroblast collagenase
Matrix metalloproteinase-1
MMP-1
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
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.
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.

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
29108
15377
PubChem 32051
271
22247451
962
1fblA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:2x_ZN Bound:3x_CA Unbound Unbound Unbound Unbound Intermediate-analogue:HTA
1aykA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:2x_ZN Bound:_CA Unbound Unbound Unbound Unbound Unbound
1cgeA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:2x_ZN Bound:3x_CA Unbound Unbound Unbound Unbound Unbound
1cgfA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:2x_ZN Bound:3x_CA Unbound Unbound Unbound Unbound Unbound
1cgfB Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:2x_ZN Bound:3x_CA Unbound Unbound Unbound Unbound Unbound
1cglA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:2x_ZN Bound:_CA Unbound Unbound Unbound Unbound Intermediate-analogue:PHQ-ABU-LEU-PHE-EMR(chain C)
1cglB Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:2x_ZN Bound:_CA Unbound Unbound Unbound Unbound Intermediate-analogue:PHQ-ABU-LEU-PHE-EMR(chain D)
1hfcA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:2x_ZN Bound:_CA Unbound Unbound Unbound Unbound Intermediate-analogue:PLH
1su3A01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:2x_ZN Bound:3x_CA Unbound Unbound Unbound Unbound Unbound
1su3B01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:2x_ZN Bound:3x_CA Unbound Unbound Unbound Unbound Unbound
2aykA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:2x_ZN Bound:_CA Unbound Unbound Unbound Unbound Unbound
2tclA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:2x_ZN Bound:2x_CA Unbound Unbound Unbound Unbound Intermediate-analogue:RO4
3aykA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:2x_ZN Bound:_CA Unbound Unbound Unbound Unbound Intermediate-analogue:CGS
4aykA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:2x_ZN Bound:_CA Unbound Unbound Unbound Unbound Intermediate-analogue:CGS
966cA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:2x_ZN Bound:3x_CA Unbound Unbound Unbound Unbound Intermediate-analogue:RS2
1fblA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Bound:_CA Unbound Unbound Unbound Unbound Unbound
1su3A02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Bound:_CA Unbound Unbound Unbound Unbound Unbound
1su3B02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain 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 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain 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 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain 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 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain 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 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain 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 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain 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 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain 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 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain 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 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain 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 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain 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 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain 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 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain 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 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain 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 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain 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 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain 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 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain 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 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1su3A02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1su3B02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain

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, four-bladed beta-propeller.
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, tissue inhibitor of metalloproteinases-1 (TIMP-1).
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, secondary structure and dynamics of the inhibitor-free catalytic fragment of human fibroblast collagenase.
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. Part 3: incorporation of basic amines.
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, all the calcium ions and one of the zinc ions are not involved in catalysis.
According to the literature [6], [8] & [9], this enzyme is partially and distantly homologous to thermolysin (D00234 in EzCatDB; CATH 3.10.170.10), although it is differently classified in the CATH database.
According to the literature [6] & [9] suggested that the catalytic zinc ion of this enzyme, which is bound to three histidine residues, might have a higher net positive charge and a greater ability to stabilize the negative charge in the transition-state than the counterpart zinc, bound to two histidine residues and an acidic residue, in thermolysin (D00234 in EzCatDB).
According to the literature [6], [8] & [9], the catalytic reaction proceeds as follows:
(1) Carbonyl oxygen of target bond and hydrolytic water molecule are bound to zinc ion, which facilitates the catalysis. Glu219 (of 1fbl) acts as a general base to deprotonate and activate the water molecule.
(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, together with the zinc ion. Here, Asn112 and mainchain carbonyl group of Ala113 stabilize the leaving amine group. The zinc ion stabilizes the negative charge on the hydroxyl anion and the new hydroxyl group (originally water).
(4) Glu219 acts as a genral acid to protonate the leaving amine group. (Glu143 may also shuttle the remaining proton from the hydroxyl group to the amine to complete the bond cleavage.)

Created Updated
2005-02-16 2009-02-26