DB code: M00101

CATH domain 3.40.390.10 : Collagenase (Catalytic Domain) Catalytic domain
2.10.10.10 : Seminal Fluid Protein PDC-109 (Domain B)
2.10.10.10 : Seminal Fluid Protein PDC-109 (Domain B)
2.10.10.10 : Seminal Fluid Protein PDC-109 (Domain B)
2.110.10.10 : Hemopexin
E.C. 3.4.24.24
CSA 1ck7 1qib
M-CSA 1ck7 1qib
MACiE

CATH domain Related DB codes (homologues)
2.110.10.10 : Hemopexin D00232
3.40.390.10 : Collagenase (Catalytic Domain) S00394 S00395 S00397 S00398 S00399 D00232 D00236

Uniprot Enzyme Name
UniprotKB Protein name Synonyms RefSeq MEROPS Pfam
P08253 72 kDa type IV collagenase
EC 3.4.24.24
72 kDa gelatinase
Matrix metalloproteinase-2
MMP-2
Gelatinase A
TBE-1
NP_001121363.1 (Protein)
NM_001127891.1 (DNA/RNA sequence)
NP_004521.1 (Protein)
NM_004530.4 (DNA/RNA sequence)
M10.003 (Metallo)
PF00040 (fn2)
PF00045 (Hemopexin)
PF00413 (Peptidase_M10)
PF01471 (PG_binding_1)
[Graphical View]

KEGG enzyme name
gelatinase A
72-kDa gelatinase
matrix metalloproteinase 2
type IV collagenase
3/4 collagenase (Obsolete)
matrix metalloproteinase 5 (Obsolete)
72 kDa gelatinase type A
collagenase IV
collagenase type IV
MMP 2
type IV collagen metalloproteinase
type IV collagenase/gelatinase
matrix metalloproteinase 2

UniprotKB: Accession Number Entry name Activity Subunit Subcellular location Cofactor
P08253 MMP2_HUMAN Cleavage of gelatin type I and collagen types IV, V, VII, X. Cleaves the collagen-like sequence Pro-Gln-Gly-|- Ile-Ala-Gly-Gln. Ligand for integrin alpha-V/beta-3. 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 C00560 C00335 C00421 C02531 C02259 C00001 C00017 C00012
E.C.
Compound Zinc Calcium Gelatin type I Collagen type IV Collagen type V Collagen type VII Collagen type X H2O Protein Peptide
Type heavy metal divalent metal (Ca2+, Mg2+) peptide/protein peptide/protein peptide/protein peptide/protein peptide/protein H2O peptide/protein peptide/protein
ChEBI 29105
 29105
 		29108
 29108
 		15377
 15377
PubChem 32051
 32051
 		271
 271
 		22247451
 962
 22247451
 962
1ck7A01 Bound:2x_ZN Bound:2x_CA Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1qibA Bound:2x_ZN Bound:3x_CA Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1gxdA01 Bound:2x_ZN Bound:_CA Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1gxdB01 Bound:2x_ZN Bound:_CA Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1eakA01 Bound:2x_ZN Bound:2x_CA Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1eakB01 Bound:2x_ZN Bound:2x_CA Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1eakC01 Bound:2x_ZN Bound:2x_CA Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1eakD01 Bound:2x_ZN Bound:2x_CA Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1ck7A02 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1gxdA02 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1gxdB02 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1eakA02 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Analogue:GLY-PRO-ALA-GLY-PRO-PRO-GLY-ALA
1eakB02 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1eakC02 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1eakD02 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Analogue:GLY-PRO-ALA-GLY-PRO-PRO-GLY-ALA
1ck7A03 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1gxdA03 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1gxdB03 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1eakA03 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1eakB03 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1eakC03 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1eakD03 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1cxwA Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1ck7A04 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1gxdA04 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1gxdB04 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1eakA04 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1eakB04 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1eakC04 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1eakD04 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1j7mA Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1ck7A05 Unbound Bound:_CA Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1gxdA05 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1gxdB05 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound

Reference for Active-site residues
resource references E.C.

Active-site residues
PDB Catalytic residues Cofactor-binding residues Modified residues Main-chain involved in catalysis Comment
1ck7A01 CYS 102;HIS 403;HIS 407;HIS 413(catalytic Zinc) mutant E404A
1qibA GLU 202 ;HIS 201;HIS 205;HIS 211(catalytic Zinc)
1gxdA01 CYS 73;HIS 374;HIS 378;HIS 384(catalytic Zinc) mutant E375A
1gxdB01 CYS 73;HIS 374;HIS 378;HIS 384(catalytic Zinc) mutant E375A
1eakA01 CYS 102;HIS 403;HIS 407;HIS 413(catalytic Zinc) mutant E404Q
1eakB01 CYS 102;HIS 403;HIS 407;HIS 413(catalytic Zinc) mutant E404Q
1eakC01 CYS 102;HIS 403;HIS 407;HIS 413(catalytic Zinc) mutant E404Q
1eakD01 CYS 102;HIS 403;HIS 407;HIS 413(catalytic Zinc) mutant E404Q
1ck7A02
1gxdA02
1gxdB02
1eakA02
1eakB02
1eakC02
1eakD02
1ck7A03
1gxdA03
1gxdB03
1eakA03
1eakB03
1eakC03
1eakD03
1cxwA
1ck7A04
1gxdA04
1gxdB04
1eakA04
1eakB04
1eakC04
1eakD04
1j7mA
1ck7A05
1gxdA05
1gxdB05

References for Catalytic Mechanism
References Sections No. of steps in catalysis
[4]
p.1667-1669

References
[1]
Resource
Comments
Medline ID
PubMed ID 7583664
Journal Nat Struct Biol
Year 1995
Volume 2
Pages 938-42
Authors Libson AM, Gittis AG, Collier IE, Marmer BL, Goldberg GI, Lattman EE
Title Crystal structure of the haemopexin-like C-terminal domain of gelatinase A.
Related PDB
Related UniProtKB
[2]
Resource
Comments
Medline ID
PubMed ID 8549817
Journal FEBS Lett
Year 1996
Volume 378
Pages 126-30
Authors Gohlke U, Gomis-Ruth FX, Crabbe T, Murphy G, Docherty AJ, Bode W
Title The C-terminal (haemopexin-like) domain structure of human gelatinase A (MMP2): structural implications for its function.
Related PDB
Related UniProtKB
[3]
Resource
Comments
Medline ID
PubMed ID
Journal Croatica Chemica Acta
Year 1999
Volume 72
Pages 575-591
Authors Dhanaraj V, Williams_MG, Ye_QZ, Molina_F, Johnson_LL, Ortwine_DF, Pavlovsky_A, Rubin_JR, Skeean_RW, White_AD, Humblet_C, Hupe_DJ, Blundell_TL
Title X-ray structure of gelatinase a catalytic domain complexed with a hydroxamate inhibitor.
Related PDB 1qib
Related UniProtKB
[4]
Resource
Comments X-ray crystallography
Medline ID
PubMed ID 10356396
Journal Science
Year 1999
Volume 284
Pages 1667-70
Authors Morgunova E, Tuuttila A, Bergmann U, Isupov M, Lindqvist Y, Schneider G, Tryggvason K
Title Structure of human pro-matrix metalloproteinase-2: activation mechanism revealed.
Related PDB 1ck7
Related UniProtKB
[5]
Resource
Comments
Medline ID
PubMed ID 10545322
Journal Structure Fold Des
Year 1999
Volume 7
Pages 1235-45
Authors Briknarova K, Grishaev A, Banyai L, Tordai H, Patthy L, Llinas M
Title The second type II module from human matrix metalloproteinase 2: structure, function and dynamics.
Related PDB 1cxw
Related UniProtKB
[6]
Resource
Comments
Medline ID
PubMed ID 11320090
Journal J Biol Chem
Year 2001
Volume 276
Pages 27613-21
Authors Briknarova K, Gehrmann M, Banyai L, Tordai H, Patthy L, Llinas M
Title Gelatin-binding region of human matrix metalloproteinase-2: solution structure, dynamics, and function of the COL-23 two-domain construct.
Related PDB 1j7m
Related UniProtKB
[7]
Resource
Comments
Medline ID
PubMed ID 11390386
Journal J Biol Chem
Year 2001
Volume 276
Pages 32966-70
Authors Williamson RA, Hutton M, Vogt G, Rapti M, Knauper V, Carr MD, Murphy G
Title Tyrosine 36 plays a critical role in the interaction of the AB loop of tissue inhibitor of metalloproteinases-2 with matrix metalloproteinase-14.
Related PDB
Related UniProtKB
[8]
Resource
Comments
Medline ID
PubMed ID 11513874
Journal FEBS Lett
Year 2001
Volume 503
Pages 158-62
Authors Patterson ML, Atkinson SJ, Knauper V, Murphy G
Title Specific collagenolysis by gelatinase A, MMP-2, is determined by the hemopexin domain and not the fibronectin-like domain.
Related PDB
Related UniProtKB
[9]
Resource
Comments
Medline ID
PubMed ID 11566806
Journal Biophys J
Year 2001
Volume 81
Pages 2370-7
Authors Collier IE, Saffarian S, Marmer BL, Elson EL, Goldberg G
Title Substrate recognition by gelatinase A: the C-terminal domain facilitates surface diffusion.
Related PDB
Related UniProtKB
[10]
Resource
Comments
Medline ID
PubMed ID 12023034
Journal FEBS Lett
Year 2002
Volume 519
Pages 147-52
Authors Lee SJ, Jang JW, Kim YM, Lee HI, Jeon JY, Kwon YG, Lee ST
Title Endostatin binds to the catalytic domain of matrix metalloproteinase-2.
Related PDB
Related UniProtKB
[11]
Resource
Comments
Medline ID
PubMed ID 12032297
Journal Proc Natl Acad Sci U S A
Year 2002
Volume 99
Pages 7414-9
Authors Morgunova E, Tuuttila A, Bergmann U, Tryggvason K
Title Structural insight into the complex formation of latent matrix metalloproteinase 2 with tissue inhibitor of metalloproteinase 2.
Related PDB 1gxd
Related UniProtKB
[12]
Resource
Comments
Medline ID
PubMed ID 12147339
Journal Biochim Biophys Acta
Year 2002
Volume 1598
Pages 10-23
Authors Feng Y, Likos JJ, Zhu L, Woodward H, Munie G, McDonald JJ, Stevens AM, Howard CP, De Crescenzo GA, Welsch D, Shieh HS, Stallings WC
Title Solution structure and backbone dynamics of the catalytic domain of matrix metalloproteinase-2 complexed with a hydroxamic acid inhibitor.
Related PDB
Related UniProtKB
[13]
Resource
Comments
Medline ID
PubMed ID 12486137
Journal J Biol Chem
Year 2003
Volume 278
Pages 12241-6
Authors Trexler M, Briknarova K, Gehrmann M, Llinas M, Patthy L
Title Peptide ligands for the fibronectin type II modules of matrix metalloproteinase 2 (MMP-2).
Related PDB
Related UniProtKB
[14]
Resource
Comments
Medline ID
PubMed ID 12642591
Journal J Biol Chem
Year 2003
Volume 278
Pages 18140-5
Authors Lauer-Fields JL, Sritharan T, Stack MS, Nagase H, Fields GB
Title Selective hydrolysis of triple-helical substrates by matrix metalloproteinase-2 and -9.
Related PDB
Related UniProtKB
[15]
Resource
Comments
Medline ID
PubMed ID 12878590
Journal J Biol Chem
Year 2003
Volume 278
Pages 38765-71
Authors Jiang A, Pei D
Title Distinct roles of catalytic and pexin-like domains in membrane-type matrix metalloproteinase (MMP)-mediated pro-MMP-2 activation and collagenolysis.
Related PDB
Related UniProtKB

Comments
This enzyme belongs to the peptidase family M10A.
Although the catalytic residue and catalytic zinc are annotated, the detailed catalytic mechanism is still unclear.

Created Updated
2002-08-27 2009-02-26