interstitial collagenase

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.{{cite journal | vauthors = Li J, Brick P, O'Hare MC, Skarzynski T, Lloyd LF, Curry VA, Clark IM, Bigg HF, Hazleman BL, Cawston TE | title = Structure of full-length porcine synovial collagenase reveals a C-terminal domain containing a calcium-linked, four-bladed beta-propeller | journal = Structure | volume = 3 | issue = 6 | pages = 541–9 | date = June 1995 | pmid = 8590015 | doi = 10.1016/S0969-2126(01)00188-5 | doi-access = free }} The primary structure of MMP-1 was first published by Goldberg, G I, et al. 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).

The catalytic domains of MMPs share very similar characteristics, having a general shape of oblate ellipsoid with a diameter of ~40 Å.{{cite journal | vauthors = Tallant C, Marrero A, Gomis-Rüth FX | title = Matrix metalloproteinases: fold and function of their catalytic domains | journal = Biochim. Biophys. Acta | volume = 1803 | issue = 1 | pages = 20–8 | date = January 2010 | pmid = 19374923 | doi = 10.1016/j.bbamcr.2009.04.003 | doi-access = free }} Despite the similarity of the catalytic domains of MMPs, this entry will focus only on the structural features of MMP-1 catalytic domain.

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.{{cite journal | vauthors = Spurlino JC, Smallwood AM, Carlton DD, Banks TM, Vavra KJ, Johnson JS, Cook ER, Falvo J, Wahl RC, Pulvino TA | title = 1.56 A structure of mature truncated human fibroblast collagenase | journal = Proteins | volume = 19 | issue = 2 | pages = 98–109 | date = June 1994 | pmid = 8090713 | doi = 10.1002/prot.340190203 | s2cid = 23973090 }}

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.

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.{{cite journal | vauthors = Maskos K, Bode W | title = Structural basis of matrix metalloproteinases and tissue inhibitors of metalloproteinases | journal = Mol. Biotechnol. | volume = 25 | issue = 3 | pages = 241–66 | date = November 2003 | pmid = 14668538 | doi = 10.1385/MB:25:3:241 | s2cid = 24110599 }} A specific region (183)RWTNNFREY(191) has been identified as a critical segment of matrix metalloproteinase 1 for the expression of collagenolytic activity.{{cite journal | vauthors = 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 | journal = J. Biol. Chem. | volume = 275 | issue = 38 | pages = 29610–7 | date = September 2000 | pmid = 10871619 | doi = 10.1074/jbc.M004039200 | doi-access = free }} 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.{{cite journal | vauthors = Bode W, Gomis-Rüth FX, Stöckler W | title = 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' | journal = FEBS Lett. | volume = 331 | issue = 1–2 | pages = 134–40 | date = September 1993 | pmid = 8405391 | doi = 10.1016/0014-5793(93)80312-I | s2cid = 27244239 | doi-access = | bibcode = 1993FEBSL.331..134B }}{{cite journal | vauthors = Stöcker W, Grams F, Baumann U, Reinemer P, Gomis-Rüth FX, McKay DB, Bode W | title = The metzincins--topological and sequential relations between the astacins, adamalysins, serralysins, and matrixins (collagenases) define a superfamily of zinc-peptidases | journal = Protein Sci. | volume = 4 | issue = 5 | pages = 823–40 | date = May 1995 | pmid = 7663339 | pmc = 2143131 | doi = 10.1002/pro.5560040502 }} 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.

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.

Mechanical force may increase the expression of MMP1 in human periodontal ligament cells.{{cite journal | vauthors = Huang SF, Li YH, Ren YJ, Cao ZG, Long X | title = 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 | journal = Eur. J. Oral Sci. | volume = 116 | issue = 4 | pages = 319–23 | date = August 2008 | pmid = 18705799 | doi = 10.1111/j.1600-0722.2008.00552.x }} During cancer progression, MMP1 can be dysregulated by different mechanisms, including the activation of an insulator element located between MMP8 and MMP10 genes.{{cite journal | vauthors = Llinàs-Arias P, Ensenyat-Mendez M, Íñiguez-Muñoz S, Orozco J, Valdez B | title = Chromatin insulation orchestrates matrix metalloproteinase gene cluster expression reprogramming in aggressive breast cancer tumors | journal = Molecular Cancer | volume = 22 | issue = 4 | date = November 2023 | page = 190 | pmid = 38017545 | doi = 10.1186/s12943-023-01906-8 | pmc = 10683115 | doi-access = free }}

MMP1 has been shown to interact with CD49b.{{cite journal | vauthors = Stricker TP, Dumin JA, Dickeson SK, Chung L, Nagase H, Parks WC, Santoro SA | title = Structural analysis of the alpha(2) integrin I domain/procollagenase-1 (matrix metalloproteinase-1) interaction | journal = J. Biol. Chem. | volume = 276 | issue = 31 | pages = 29375–81 | date = August 2001 | pmid = 11359774 | doi = 10.1074/jbc.M102217200 | doi-access = free }}{{cite journal | vauthors = Dumin JA, Dickeson SK, Stricker TP, Bhattacharyya-Pakrasi M, Roby JD, Santoro SA, Parks WC | title = Pro-collagenase-1 (matrix metalloproteinase-1) binds the alpha(2)beta(1) integrin upon release from keratinocytes migrating on type I collagen | journal = J. Biol. Chem. | volume = 276 | issue = 31 | pages = 29368–74 | date = August 2001 | pmid = 11359786 | doi = 10.1074/jbc.M104179200 | doi-access = free }}

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• {{cite journal | vauthors = Krane SM | title = Is collagenase (matrix metalloproteinase-1) necessary for bone and other connective tissue remodeling? | journal = Clin. Orthop. Relat. Res. | issue = 313 | pages = 47–53 | year = 1995 | pmid = 7641497 }}
• {{cite journal | vauthors = Massova I, Kotra LP, Fridman R, Mobashery S | title = Matrix metalloproteinases: structures, evolution, and diversification | journal = FASEB J. | volume = 12 | issue = 25n26 | pages = 1075–95 | year = 1998 | pmid = 9737711 | doi = 10.1142/S0217984998001256 | citeseerx = 10.1.1.31.3959 }}
• {{cite journal | vauthors = Nagase H, Woessner JF | title = Matrix metalloproteinases | journal = J. Biol. Chem. | volume = 274 | issue = 31 | pages = 21491–4 | year = 1999 | pmid = 10419448 | doi = 10.1074/jbc.274.31.21491 | doi-access = free }}
• {{cite journal | vauthors = Okada Y, Hashimoto G | title = [Degradation of extracellular matrix by matrix metalloproteinases and joint destruction] | journal = Seikagaku | volume = 73 | issue = 11 | pages = 1309–21 | year = 2001 | pmid = 11831026 }}
• {{cite journal | vauthors = Seiki M | title = Membrane-type 1 matrix metalloproteinase: a key enzyme for tumor invasion | journal = Cancer Lett. | volume = 194 | issue = 1 | pages = 1–11 | year = 2003 | pmid = 12706853 | doi = 10.1016/S0304-3835(02)00699-7 }}
• {{cite journal | vauthors = Golubkov VS, Strongin AY | title = Proteolysis-driven oncogenesis | journal = Cell Cycle | volume = 6 | issue = 2 | pages = 147–50 | year = 2007 | pmid = 17245132 | doi = 10.4161/cc.6.2.3706 | doi-access = free }}

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• The MEROPS online database for peptidases and their inhibitors: [http://merops.sanger.ac.uk/cgi-bin/merops.cgi?id=M10.001 M10.001]
• {{PDBe-KB2|P03956|Interstitial collagenase}}

{{PDB Gallery|geneid=4312}}

{{Metalloendopeptidases}}

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Category:Matrix metalloproteinases

Category:EC 3.4.24