Interstitial collagenase

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interstitial collagenase
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Interstitial collagenase, also known as fibroblast collagenase and matrix metalloproteinase-1 (MMP-1), is an enzyme that in humans is encoded by the MMP1 gene. [1] [2] [3] [4] The gene is part of a cluster of MMP genes which localize to chromosome 11q22.3. [2] MMP-1 was the first vertebrate collagenase both purified to homogeneity as a protein, and cloned as a cDNA. [5] [6] MMP-1 has an estimated molecular mass of 54 kDa. [7]

Contents

Structure

MMP-1 has an archetypal structure consisting of a pre-domain, a pro-domain, a catalytic domain, a linker region and a hemopexin-like domain. [8] The primary structure of MMP-1 was first published by Goldberg, G I, et al. [6] Two main nomenclatures for the primary structure are currently in use, the original one from which the first amino-acid starts with the signalling peptide and a second one where the first amino-acid starts counting from the prodomain (proenzyme nomenclature).

Catalytic domain

The catalytic domains of MMPs share very similar characteristics, having a general shape of oblate ellipsoid with a diameter of ~40 Å. [9] Despite the similarity of the catalytic domains of MMPs, this entry will focus only on the structural features of MMP-1 catalytic domain.

Overall structural characteristics

The catalytic domain of MMP-1 is composed of five highly twisted β-strands (sI-sV), three α-helix (hA-hC) and a total of eight loops, enclosing a total of five metal ions, three Ca2+ and two Zn2+, one of which with catalytic role. [10]

The catalytic domain (CAT) of MMP-1 starts with the F100 (non-truncated CAT) as the first amino-acid of the N-terminal loop of the CAT domain. The first published x-ray structure of the CAT domain was representative of the truncated form of this domain, where the first 7 amino-acids are not present. [10]

After the initial loop, the sequences follows to the first and longest β-sheet (sI). A second loop precedes large "amphipathic α-helix" (hA) that longitudinally spans protein site. The β-strands sII and sIII follows separated by the respective loops, loop 4 being commonly designated as "short loop" bridging sII to sIII. Following the sIII strand the sequence meets the 'S-shaped double loop' that is of primary importance for the peptide structure and catalytic activity (see further) as it extends to the cleft side "bulge", continuing to the only antiparallel β-strand sIV, which is prime importance for binding peptidic substrates or inhibitors by forming main chain hydrogen bond. Following sIV, loop Gln186-Gly192 and β-strand sV are responsible for contributing with many ligands to the several metal ions present in the protein (read further). A large open loop follows sV which has proven importance in substrate specificity within the MMPs family. [11] A specific region (183)RWTNNFREY(191) has been identified as a critical segment of matrix metalloproteinase 1 for the expression of collagenolytic activity. [12] On C-terminal part of the CAT Domain the hB α-helix, known as the "active-site helix" encompasses part of the "zinc-binding consensus sequence" HEXXHXXGXXH that is characteristic of the Metzincin superfamily. [13] [14] The α-helix hB finishes abruptly at Gly225 where the last loop of the domain starts. This last loop contains the "specificity loop" which is the shortest in the MMPs family. The Catalytic Domain ends at Gly261 with α-helix hC.

Function

MMPs are involved in the breakdown of extracellular matrix in normal physiological processes, such as embryonic development, reproduction, and tissue remodeling, as well as in disease processes, such as arthritis and metastasis. Specifically, MMP-1 breaks down the interstitial collagens, types I, II, and III.

Induction of matrix metalloproteinase 1 in rat corneas by ciprofloxacin, ofloxacin and levofloxacin (b,c,d) compared to artificial tears (a). Reviglio et al., 2003. Matrix metalloproteinase in rat cornea after artificial tears Ciprofloxacin Ofloxacin Levofloxacin.jpg
Induction of matrix metalloproteinase 1 in rat corneas by ciprofloxacin, ofloxacin and levofloxacin (b,c,d) compared to artificial tears (a). Reviglio et al., 2003.

Regulation

Mechanical force may increase the expression of MMP1 in human periodontal ligament cells. [15] During cancer progression, MMP1 can be dysregulated by different mechanisms, including the activation of an insulator element located between MMP8 and MMP10 genes. [16]

Interactions

MMP1 has been shown to interact with CD49b. [17] [18]

Related Research Articles

Matrix metalloproteinases (MMPs), also known as matrix metallopeptidases or matrixins, are metalloproteinases that are calcium-dependent zinc-containing endopeptidases; other family members are adamalysins, serralysins, and astacins. The MMPs belong to a larger family of proteases known as the metzincin superfamily.

Gelatinases are enzymes capable of degrading gelatin through hydrolysis, playing a major role in degradation of extracellular matrix and tissue remodeling. Gelatinases are a type of matrix metalloproteinases (MMPs), a family of enzymes that depend on zinc as a cofactor and can break down parts of the extracellular matrix. MMPs have multiple subgroups, including Gelatinase A and Gelatinase B. Gelatinases are composed of a variety of EC numbers: Gelatinase A uses 3.4.24.24, and Gelatinase B uses 3.4.24.35, in which the first three numbers are same. The first digit, 3, is the class. Class 3 enzymes are hydrolases, enzymes that catalyze hydrolysis reactions, that is, they cleave bonds in presence of water. Next digit is sub-class 4, or proteases, which are enzymes who hydrolyze peptide bonds in proteins. The next number is the sub-subclass of 24, which consists of metalloendopeptidases which contain metal ions in their active sites, in this case zinc, helping in cleavage of peptide bonds. The last part of the EC number is the serial number, identifying specific enzymes within a sub-subclass. 24 represents gelatinase A, which is a metalloproteinase that breaks down gelatin and collagen, while 35 represents Gelatinase B, which hydrolyzes peptide bonds.

Microbial collagenase is an enzyme. This enzyme catalyses the following chemical reaction

<span class="mw-page-title-main">MMP9</span> Protein-coding gene in the species Homo sapiens

Matrix metallopeptidase 9 (MMP-9), also known as 92 kDa type IV collagenase, 92 kDa gelatinase or gelatinase B (GELB), is a matrixin, a class of enzymes that belong to the zinc-metalloproteinases family involved in the degradation of the extracellular matrix. In humans the MMP9 gene encodes for a signal peptide, a propeptide, a catalytic domain with inserted three repeats of fibronectin type II domain followed by a C-terminal hemopexin-like domain.

<span class="mw-page-title-main">MMP2</span> Protein-coding gene in the species Homo sapiens

72 kDa type IV collagenase also known as matrix metalloproteinase-2 (MMP-2) and gelatinase A is an enzyme that in humans is encoded by the MMP2 gene. The MMP2 gene is located on chromosome 16 at position 12.2.

<span class="mw-page-title-main">MMP14</span> Protein-coding gene in the species Homo sapiens

Matrix metalloproteinase-14 is an enzyme that in humans is encoded by the MMP14 gene.

<span class="mw-page-title-main">MMP3</span>

Stromelysin-1 also known as matrix metalloproteinase-3 (MMP-3) is an enzyme that in humans is encoded by the MMP3 gene. The MMP3 gene is part of a cluster of MMP genes which localize to chromosome 11q22.3. MMP-3 has an estimated molecular weight of 54 kDa.

<span class="mw-page-title-main">TIMP2</span> Protein-coding gene in the species Homo sapiens

Tissue inhibitor of metalloproteinases 2 (TIMP2) is a gene and a corresponding protein. The gene is a member of the TIMP gene family. The protein is thought to be a metastasis suppressor.

<span class="mw-page-title-main">MMP7</span> Protein-coding gene in humans

Matrilysin also known as matrix metalloproteinase-7 (MMP-7), pump-1 protease (PUMP-1), or uterine metalloproteinase is an enzyme in humans that is encoded by the MMP7 gene. The enzyme has also been known as matrin, putative metalloproteinase-1, matrix metalloproteinase pump 1, PUMP-1 proteinase, PUMP, metalloproteinase pump-1, putative metalloproteinase, MMP). Human MMP-7 has a molecular weight around 30 kDa.

<span class="mw-page-title-main">Matrix metallopeptidase 13</span> Protein-coding gene in the species Homo sapiens

Collagenase 3 is an enzyme that in humans is encoded by the MMP13 gene. It is a member of the matrix metalloproteinase (MMP) family. Like most MMPs, it is secreted as an inactive pro-form. MMP-13 has an predicted molecular weight around 54 kDa. It is activated once the pro-domain is cleaved, leaving an active enzyme composed of the catalytic domain and the hemopexin-like domain PDB: 1PEX​. Although the actual mechanism has not been described, the hemopexin domain participates in collagen degradation, the catalytic domain alone being particularly inefficient in collagen degradation. During embryonic development, MMP-13 is expressed in the skeleton as required for restructuring the collagen matrix for bone mineralization. In pathological situations it is highly overexpressed; this occurs in human carcinomas, rheumatoid arthritis and osteoarthritis.

<span class="mw-page-title-main">Matrix metallopeptidase 12</span> Enzyme involved in breakdown of extracellular matrix, encoded for by the MMP12 gene in humans

Matrix metalloproteinase-12 (MMP-12) also known as macrophage metalloelastase (MME) or macrophage elastase (ME) is an enzyme that in humans is encoded by the MMP12 gene.

<span class="mw-page-title-main">MMP26</span> Protein-coding gene in the species Homo sapiens

Matrix metalloproteinase-26 also known as matrilysin-2 and endometase is an enzyme that in humans is encoded by the MMP26 gene.

<span class="mw-page-title-main">MMP19</span> Protein-coding gene in the species Homo sapiens

Matrix metalloproteinase-19 (MMP-19) also known as matrix metalloproteinase RASI is an enzyme that in humans is encoded by the MMP19 gene.

<span class="mw-page-title-main">MMP16</span> Protein-coding gene in the species Homo sapiens

Matrix metalloproteinase-16 is an enzyme that in humans is encoded by the MMP16 gene.

<span class="mw-page-title-main">TIMP4</span> Protein-coding gene in the species Homo sapiens

Metalloproteinase inhibitor 4 is an enzyme that in humans is encoded by the TIMP4 gene.

<span class="mw-page-title-main">MMP17</span> Protein-coding gene in the species Homo sapiens

Matrix metalloproteinase-17 (MMP-17) also known as membrane-type matrix metalloproteinase 4 is an enzyme that in humans is encoded by the MMP17 gene.

<span class="mw-page-title-main">MMP25</span> Protein-coding gene in the species Homo sapiens

Matrix metalloproteinase-25 is an enzyme that in humans is encoded by the MMP25 gene.

<span class="mw-page-title-main">MMP8</span> Protein-coding gene in the species Homo sapiens

Neutrophil collagenase, also known as matrix metalloproteinase-8 (MMP-8) or PMNL collagenase (MNL-CL), is a collagen cleaving enzyme which is present in the connective tissue of most mammals. In humans, the MMP-8 protein is encoded by the MMP8 gene. The gene is part of a cluster of MMP genes which localize to chromosome 11q22.3. Most MMP's are secreted as inactive proproteins which are activated when cleaved by extracellular proteinases. However, the enzyme encoded by this gene is stored in secondary granules within neutrophils and is activated by autolytic cleavage.

<span class="mw-page-title-main">MMP27</span> Protein-coding gene in the species Homo sapiens

Matrix metallopeptidase 27 also known as MMP-27 is an enzyme which in humans is encoded by the MMP27 gene.

Transforming growth factor beta (TGF-β) is a potent cell regulatory polypeptide homodimer of 25kD. It is a multifunctional signaling molecule with more than 40 related family members. TGF-β plays a role in a wide array of cellular processes including early embryonic development, cell growth, differentiation, motility, and apoptosis.

References

  1. ↑ "UniProt". www.uniprot.org. Retrieved 17 July 2022.
  2. 1 2 EntrezGene 4312
  3. ↑ Brinckerhoff CE, Ruby PL, Austin SD, Fini ME, White HD (February 1987). "Molecular cloning of human synovial cell collagenase and selection of a single gene from genomic DNA". J. Clin. Invest. 79 (2): 542–6. doi:10.1172/JCI112845. PMC   424122 . PMID   3027129.
  4. ↑ Pendás AM, Santamaría I, Alvarez MV, Pritchard M, López-Otín C (October 1996). "Fine physical mapping of the human matrix metalloproteinase genes clustered on chromosome 11q22.3". Genomics. 37 (2): 266–8. doi:10.1006/geno.1996.0557. PMID   8921407.
  5. ↑ Gross J, Lapiere CM (June 1962). "Collagenolytic activity in amphibian tissues: a tissue culture assay". Proc. Natl. Acad. Sci. U.S.A. 48 (6): 1014–22. Bibcode:1962PNAS...48.1014G. doi: 10.1073/pnas.48.6.1014 . PMC   220898 . PMID   13902219.
  6. 1 2 Goldberg GI, Wilhelm SM, Kronberger A, Bauer EA, Grant GA, Eisen AZ (May 1986). "Human fibroblast collagenase. Complete primary structure and homology to an oncogene transformation-induced rat protein". J. Biol. Chem. 261 (14): 6600–5. doi: 10.1016/S0021-9258(19)84605-7 . PMID   3009463.
  7. ↑ "26585-1-AP". www.ptglab.com. Retrieved 2021-10-05.
  8. ↑ Li J, Brick P, O'Hare MC, Skarzynski T, Lloyd LF, Curry VA, Clark IM, Bigg HF, Hazleman BL, Cawston TE (June 1995). "Structure of full-length porcine synovial collagenase reveals a C-terminal domain containing a calcium-linked, four-bladed beta-propeller". Structure. 3 (6): 541–9. doi: 10.1016/S0969-2126(01)00188-5 . PMID   8590015.
  9. ↑ Tallant C, Marrero A, Gomis-Rüth FX (January 2010). "Matrix metalloproteinases: fold and function of their catalytic domains". Biochim. Biophys. Acta. 1803 (1): 20–8. doi: 10.1016/j.bbamcr.2009.04.003 . PMID   19374923.
  10. 1 2 Spurlino JC, Smallwood AM, Carlton DD, Banks TM, Vavra KJ, Johnson JS, Cook ER, Falvo J, Wahl RC, Pulvino TA (June 1994). "1.56 A structure of mature truncated human fibroblast collagenase". Proteins. 19 (2): 98–109. doi:10.1002/prot.340190203. PMID   8090713. S2CID   23973090.
  11. ↑ Maskos K, Bode W (November 2003). "Structural basis of matrix metalloproteinases and tissue inhibitors of metalloproteinases". Mol. Biotechnol. 25 (3): 241–66. doi:10.1385/MB:25:3:241. PMID   14668538. S2CID   24110599.
  12. ↑ Chung L, Shimokawa K, Dinakarpandian D, Grams F, Fields GB, Nagase H (September 2000). "Identification of the (183)RWTNNFREY(191) region as a critical segment of matrix metalloproteinase 1 for the expression of collagenolytic activity". J. Biol. Chem. 275 (38): 29610–7. doi: 10.1074/jbc.M004039200 . PMID   10871619.
  13. ↑ Bode W, Gomis-Rüth FX, Stöckler W (September 1993). "Astacins, serralysins, snake venom and matrix metalloproteinases exhibit identical zinc-binding environments (HEXXHXXGXXH and Met-turn) and topologies and should be grouped into a common family, the 'metzincins'". FEBS Lett. 331 (1–2): 134–40. doi:10.1016/0014-5793(93)80312-I. PMID   8405391. S2CID   27244239.
  14. ↑ Stöcker W, Grams F, Baumann U, Reinemer P, Gomis-Rüth FX, McKay DB, Bode W (May 1995). "The metzincins--topological and sequential relations between the astacins, adamalysins, serralysins, and matrixins (collagenases) define a superfamily of zinc-peptidases". Protein Sci. 4 (5): 823–40. doi:10.1002/pro.5560040502. PMC   2143131 . PMID   7663339.
  15. ↑ Huang SF, Li YH, Ren YJ, Cao ZG, Long X (August 2008). "The effect of a single nucleotide polymorphism in the matrix metalloproteinase-1 (MMP-1) promoter on force-induced MMP-1 expression in human periodontal ligament cells". Eur. J. Oral Sci. 116 (4): 319–23. doi:10.1111/j.1600-0722.2008.00552.x. PMID   18705799.
  16. ↑ Llinàs-Arias P, Ensenyat-Mendez M, Íñiguez-Muñoz S, Orozco J, Valdez B (November 2023). "Chromatin insulation orchestrates matrix metalloproteinase gene cluster expression reprogramming in aggressive breast cancer tumors". Molecular Cancer. 22 (4): 190. doi: 10.1186/s12943-023-01906-8 . PMC   10683115 . PMID   38017545.
  17. ↑ Stricker TP, Dumin JA, Dickeson SK, Chung L, Nagase H, Parks WC, Santoro SA (August 2001). "Structural analysis of the alpha(2) integrin I domain/procollagenase-1 (matrix metalloproteinase-1) interaction". J. Biol. Chem. 276 (31): 29375–81. doi: 10.1074/jbc.M102217200 . PMID   11359774.
  18. ↑ Dumin JA, Dickeson SK, Stricker TP, Bhattacharyya-Pakrasi M, Roby JD, Santoro SA, Parks WC (August 2001). "Pro-collagenase-1 (matrix metalloproteinase-1) binds the alpha(2)beta(1) integrin upon release from keratinocytes migrating on type I collagen". J. Biol. Chem. 276 (31): 29368–74. doi: 10.1074/jbc.M104179200 . PMID   11359786.

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