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PDBsum entry 1pex

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protein ligands metals links
Metalloprotease PDB id
1pex
Jmol PyMol
Contents
Protein chain
192 a.a. *
Ligands
SO4
Metals
_CL ×2
_CA ×2
Waters ×73
* Residue conservation analysis
PDB id:
1pex
Name: Metalloprotease
Title: Collagenase-3 (mmp-13) c-terminal hemopexin-like domain
Structure: Collagenase-3. Chain: a. Fragment: c-terminal hemopexin-like domain. Synonym: mmp-13. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Organ: breast. Tissue: breast cancer. Expressed in: mus musculus. Expression_system_taxid: 10090. Expression_system_cell: 1pex cells. Expression_system_organelle: purified from serum free
Resolution:
2.70Å     R-factor:   0.195    
Authors: F.X.Gomis-Ruth,U.Gohlke,M.Betz,V.Knauper,G.Murphy,C.Lopez- Otin,W.Bode
Key ref:
F.X.Gomis-Rüth et al. (1996). The helping hand of collagenase-3 (MMP-13): 2.7 A crystal structure of its C-terminal haemopexin-like domain. J Mol Biol, 264, 556-566. PubMed id: 8969305 DOI: 10.1006/jmbi.1996.0661
Date:
24-May-96     Release date:   23-Dec-96    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P45452  (MMP13_HUMAN) -  Collagenase 3
Seq:
Struc:
471 a.a.
192 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.3.4.24.-  - ?????
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     extracellular region   1 term 
  Biological process     collagen catabolic process   2 terms 
  Biochemical function     metalloendopeptidase activity     1 term  

 

 
DOI no: 10.1006/jmbi.1996.0661 J Mol Biol 264:556-566 (1996)
PubMed id: 8969305  
 
 
The helping hand of collagenase-3 (MMP-13): 2.7 A crystal structure of its C-terminal haemopexin-like domain.
F.X.Gomis-Rüth, U.Gohlke, M.Betz, V.Knäuper, G.Murphy, C.López-Otín, W.Bode.
 
  ABSTRACT  
 
Collagenase-3 (MMP-13) is a matrix metalloproteinase involved in human breast cancer pathology and in arthritic processes. The crystal structure of its C-terminal haemopexin-like domain has been solved by molecular replacement and refined to an R-value of 0.195 using data to 2.7 A resolution. This structure reveals a disk-like shape. The chain is folded into a beta-propeller structure of pseudo 4-fold symmetry, with the four propeller blades arranged around a funnel-like tunnel. This central tunnel tube harbours four ions assigned as two calcium and two chloride ions. The C-terminal domain of collagenase-3 has a similar structure to the equivalent domain of gelatinase A and fibroblast collagenase 1; however, its detailed structure and surface charge pattern has a somewhat greater similarity to the latter, in agreement with the subgrouping of MMP-13 with the collagenase subfamily of MMPs. It is proposed that several small structural differences may act together to confer the characteristic binding and cleavage specificities of collagenases for triple-helical substrates, probably in co-operation with a fitting interdomain linker.
 
  Selected figure(s)  
 
Figure 1.
Figure 1. Stereo ribbon plot of MMP-13 CTD shown against the exit side of the disk. The CTD disk is slightly tilted with respect to the central pseudo 4-fold symmetry axis of the b-propeller structure to clarify the tracing of the ions in the central funnel-like tunnel. The four propeller blades are numbered (I to IV), and the four assigned ions in the tunnel are displayed as spheres (green for chloride anions, red for calcium cations; the relative radii of the spheres correspond to the different ionic radii of both species) and are labelled, as well as the N and the C terminus. The location of the b-bulges in blades II and III is further indicated. b-Strands are displayed as blue arrows, helical segments as red helices. The disulphide bond clamping the C terminus to blade I (Cys278--Cys466) is shown in CPK-fashion.
Figure 5.
Figure 5. Front view facing the entry sides superimposed with a solid Connolly surface of the CTDs of MMP-13 (a), MMP-1 (b), and MMP-2 (c). The calculations and graphical representations were perfomed with GRASP. Red patches characterize negatively charged surface patches and blue highlights positively charged patches. The electrostatic potentials were contoured from -10 (intense red) to 10 kBT/e (intense blue). The calcium ion KA502 at the tunnel entrance has been included in the calculations providing a highly positively charged surface that neutralizes the acidic side-chains of the liganding aspartate residues. Orientation as in Figure 1 additionally rotated for about 180° around a vertical axis. The four propeller blades are numbered (I to IV).
 
  The above figures are reprinted by permission from Elsevier: J Mol Biol (1996, 264, 556-566) copyright 1996.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21193411 A.Tochowicz, P.Goettig, R.Evans, R.Visse, Y.Shitomi, R.Palmisano, N.Ito, K.Richter, K.Maskos, D.Franke, D.Svergun, H.Nagase, W.Bode, and Y.Itoh (2011).
The Dimer Interface of the Membrane Type 1 Matrix Metalloproteinase Hemopexin Domain: CRYSTAL STRUCTURE AND BIOLOGICAL FUNCTIONS.
  J Biol Chem, 286, 7587-7600.
PDB code: 3c7x
21044079 E.M.Kim, and O.Hwang (2011).
Role of matrix metalloproteinase-3 in neurodegeneration.
  J Neurochem, 116, 22-32.  
20824169 R.Kothapalli, A.M.Khan, Basappa, A.Gopalsamy, Y.S.Chong, and L.Annamalai (2010).
Cheminformatics-based drug design approach for identification of inhibitors targeting the characteristic residues of MMP-13 hemopexin domain.
  PLoS One, 5, e12494.  
19615667 E.Lausch, R.Keppler, K.Hilbert, V.Cormier-Daire, S.Nikkel, G.Nishimura, S.Unger, J.Spranger, A.Superti-Furga, and B.Zabel (2009).
Mutations in MMP9 and MMP13 determine the mode of inheritance and the clinical spectrum of metaphyseal anadysplasia.
  Am J Hum Genet, 85, 168-178.  
19388774 K.E.Wyatt, J.W.Bourne, and P.A.Torzilli (2009).
Deformation-Dependent Enzyme Mechanokinetic Cleavage of Type I Collagen.
  J Biomech Eng, 131, 051004.  
19719408 T.Ueno, T.Nakaoka, H.Takeuchi, and T.Kubo (2009).
Differential gene expression in the hypopharyngeal glands of worker honeybees (Apis mellifera L.) associated with an age-dependent role change.
  Zoolog Sci, 26, 557-563.  
19700767 V.Tillgren, P.Onnerfjord, L.Haglund, and D.Heinegård (2009).
The tyrosine sulfate-rich domains of the LRR proteins fibromodulin and osteoadherin bind motifs of basic clusters in a variety of heparin-binding proteins, including bioactive factors.
  J Biol Chem, 284, 28543-28553.  
18619669 G.Murphy, and H.Nagase (2008).
Progress in matrix metalloproteinase research.
  Mol Aspects Med, 29, 290-308.  
18287018 S.Perumal, O.Antipova, and J.P.Orgel (2008).
Collagen fibril architecture, domain organization, and triple-helical conformation govern its proteolysis.
  Proc Natl Acad Sci U S A, 105, 2824-2829.  
15611040 D.Jozic, G.Bourenkov, N.H.Lim, R.Visse, H.Nagase, W.Bode, and K.Maskos (2005).
X-ray structure of human proMMP-1: new insights into procollagenase activation and collagen binding.
  J Biol Chem, 280, 9578-9585.
PDB code: 1su3
16000300 D.K.Rhee, J.Marcelino, S.Al-Mayouf, D.K.Schelling, C.F.Bartels, Y.Cui, R.Laxer, R.Goldbach-Mansky, and M.L.Warman (2005).
Consequences of disease-causing mutations on lubricin protein synthesis, secretion, and post-translational processing.
  J Biol Chem, 280, 31325-31332.  
16211490 D.M.Jacobs, S.Grimme, B.Elshorst, B.Pescatore, M.Vogtherr, M.Betz, U.Schieborr, T.Langer, K.Saxena, H.Schwalbe, and K.Fiebig (2005).
Backbone NMR assignment of the C-terminal haemopexin-like domain (HPLD) of human matrix metalloproteinase MMP-13.
  J Biomol NMR, 32, 337.  
15533938 G.R.Pelman, C.J.Morrison, and C.M.Overall (2005).
Pivotal molecular determinants of peptidic and collagen triple helicase activities reside in the S3' subsite of matrix metalloproteinase 8 (MMP-8): the role of hydrogen bonding potential of ASN188 and TYR189 and the connecting cis bond.
  J Biol Chem, 280, 2370-2377.  
15292230 E.M.Tam, T.R.Moore, G.S.Butler, and C.M.Overall (2004).
Characterization of the distinct collagen binding, helicase and cleavage mechanisms of matrix metalloproteinase 2 and 14 (gelatinase A and MT1-MMP): the differential roles of the MMP hemopexin c domains and the MMP-2 fibronectin type II modules in collagen triple helicase activities.
  J Biol Chem, 279, 43336-43344.  
15257288 L.Chung, D.Dinakarpandian, N.Yoshida, J.L.Lauer-Fields, G.B.Fields, R.Visse, and H.Nagase (2004).
Collagenase unwinds triple-helical collagen prior to peptide bond hydrolysis.
  EMBO J, 23, 3020-3030.  
15273299 S.Y.Reddy, and T.C.Bruice (2004).
Determination of enzyme mechanisms by molecular dynamics: studies on quinoproteins, methanol dehydrogenase, and soluble glucose dehydrogenase.
  Protein Sci, 13, 1965-1978.  
12656997 V.J.Uitto, C.M.Overall, and C.McCulloch (2003).
Proteolytic host cell enzymes in gingival crevice fluid.
  Periodontol 2000, 31, 77.  
12032297 E.Morgunova, A.Tuuttila, U.Bergmann, and K.Tryggvason (2002).
Structural insight into the complex formation of latent matrix metalloproteinase 2 with tissue inhibitor of metalloproteinase 2.
  Proc Natl Acad Sci U S A, 99, 7414-7419.
PDB code: 1gxd
12384502 E.Roeb, K.Schleinkofer, T.Kernebeck, S.Pötsch, B.Jansen, I.Behrmann, S.Matern, and J.Grötzinger (2002).
The matrix metalloproteinase 9 (mmp-9) hemopexin domain is a novel gelatin binding domain and acts as an antagonist.
  J Biol Chem, 277, 50326-50332.  
12042069 E.Tolosano, and F.Altruda (2002).
Hemopexin: structure, function, and regulation.
  DNA Cell Biol, 21, 297-306.  
12114504 G.Hashimoto, I.Inoki, Y.Fujii, T.Aoki, E.Ikeda, and Y.Okada (2002).
Matrix metalloproteinases cleave connective tissue growth factor and reactivate angiogenic activity of vascular endothelial growth factor 165.
  J Biol Chem, 277, 36288-36295.  
11532942 Y.Itoh, A.Takamura, N.Ito, Y.Maru, H.Sato, N.Suenaga, T.Aoki, and M.Seiki (2001).
Homophilic complex formation of MT1-MMP facilitates proMMP-2 activation on the cell surface and promotes tumor cell invasion.
  EMBO J, 20, 4782-4793.  
10675720 A.M.Pendás, J.A.Uría, M.G.Jiménez, M.Balbín, J.P.Freije, and C.López-Otín (2000).
An overview of collagenase-3 expression in malignant tumors and analysis of its potential value as a target in antitumor therapies.
  Clin Chim Acta, 291, 137-155.  
10947989 G.A.McQuibban, J.H.Gong, E.M.Tam, C.A.McCulloch, I.Clark-Lewis, and C.M.Overall (2000).
Inflammation dampened by gelatinase A cleavage of monocyte chemoattractant protein-3.
  Science, 289, 1202-1206.  
10713532 I.Broutin-L'Hermite, M.Ries-Kautt, and A.Ducruix (2000).
1.7 A x-ray structure of space-grown collagenase crystals.
  Acta Crystallogr D Biol Crystallogr, 56, 376-378.  
10662694 J.Ottl, D.Gabriel, G.Murphy, V.Knäuper, Y.Tominaga, H.Nagase, M.Kröger, H.Tschesche, W.Bode, and L.Moroder (2000).
Recognition and catabolism of synthetic heterotrimeric collagen peptides by matrix metalloproteinases.
  Chem Biol, 7, 119-132.  
10753905 L.L.Johnson, A.G.Pavlovsky, A.R.Johnson, J.A.Janowicz, C.F.Man, D.F.Ortwine, C.F.Purchase, A.D.White, and D.J.Hupe (2000).
A rationalization of the acidic pH dependence for stromelysin-1 (Matrix metalloproteinase-3) catalysis and inhibition.
  J Biol Chem, 275, 11026-11033.  
10644727 M.W.Olson, M.M.Bernardo, M.Pietila, D.C.Gervasi, M.Toth, L.P.Kotra, I.Massova, S.Mobashery, and R.Fridman (2000).
Characterization of the monomeric and dimeric forms of latent and active matrix metalloproteinase-9. Differential rates for activation by stromelysin 1.
  J Biol Chem, 275, 2661-2668.  
11004411 S.J.Crennell, P.M.Tickler, D.J.Bowen, and R.H.ffrench-Constant (2000).
The predicted structure of photopexin from Photorhabdus shows the first haemopexin-like motif in prokaryotes.
  FEMS Microbiol Lett, 191, 139-144.  
10037735 A.D.Gibson, J.A.Lamerdin, P.Zhuang, K.Baburaj, E.H.Serpersu, and C.B.Peterson (1999).
Orientation of heparin-binding sites in native vitronectin. Analyses of ligand binding to the primary glycosaminoglycan-binding site indicate that putative secondary sites are not functional.
  J Biol Chem, 274, 6432-6442.  
  10217773 C.M.Jung, O.Matsushita, S.Katayama, J.Minami, J.Sakurai, and A.Okabe (1999).
Identification of metal ligands in the Clostridium histolyticum ColH collagenase.
  J Bacteriol, 181, 2816-2822.  
10356396 E.Morgunova, A.Tuuttila, U.Bergmann, M.Isupov, Y.Lindqvist, G.Schneider, and K.Tryggvason (1999).
Structure of human pro-matrix metalloproteinase-2: activation mechanism revealed.
  Science, 284, 1667-1670.
PDB code: 1ck7
9988691 G.Velasco, A.M.Pendás, A.Fueyo, V.Knäuper, G.Murphy, and C.López-Otín (1999).
Cloning and characterization of human MMP-23, a new matrix metalloproteinase predominantly expressed in reproductive tissues and lacking conserved domains in other family members.
  J Biol Chem, 274, 4570-4576.  
10419448 H.Nagase, and J.F.Woessner (1999).
Matrix metalloproteinases.
  J Biol Chem, 274, 21491-21494.  
10607670 V.Fülöp, and D.T.Jones (1999).
Beta propellers: structural rigidity and functional diversity.
  Curr Opin Struct Biol, 9, 715-721.  
10415721 W.Bode, C.Fernandez-Catalan, F.Grams, F.X.Gomis-Rüth, H.Nagase, H.Tschesche, and K.Maskos (1999).
Insights into MMP-TIMP interactions.
  Ann N Y Acad Sci, 878, 73-91.  
9822215 C.Benaud, R.B.Dickson, and E.W.Thompson (1998).
Roles of the matrix metalloproteinases in mammary gland development and cancer.
  Breast Cancer Res Treat, 50, 97.  
9331419 E.G.Huizinga, R.Martijn van der Plas, J.Kroon, J.J.Sixma, and P.Gros (1997).
Crystal structure of the A3 domain of human von Willebrand factor: implications for collagen binding.
  Structure, 5, 1147-1156.
PDB code: 1atz
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB code is shown on the right.

 

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