PDBsum entry 1slm

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Hydrolase PDB id
Protein chain
226 a.a. *
_CA ×2
_ZN ×2
Waters ×355
* Residue conservation analysis
PDB id:
Name: Hydrolase
Title: Crystal structure of fibroblast stromelysin-1: thE C-truncat proenzyme
Structure: Stromelysin-1. Chain: a. Fragment: propeptide, catalytic. Synonym: matrix metalloproteinase-3, proteoglycanase. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Cell: fibroblast. Expressed in: escherichia coli. Expression_system_taxid: 562
1.90Å     R-factor:   0.218     R-free:   0.256
Authors: J.W.Becker
Key ref:
J.W.Becker et al. (1995). Stromelysin-1: three-dimensional structure of the inhibited catalytic domain and of the C-truncated proenzyme. Protein Sci, 4, 1966-1976. PubMed id: 8535233 DOI: 10.1002/pro.5560041002
03-Aug-95     Release date:   17-Dec-96    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
P08254  (MMP3_HUMAN) -  Stromelysin-1
477 a.a.
226 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.  - Stromelysin 1.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: Preferential cleavage where P1', P2' and P3' are hydrophobic residues.
      Cofactor: Ca(2+); Zn(2+)
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     extracellular matrix   1 term 
  Biological process     proteolysis   1 term 
  Biochemical function     metallopeptidase activity     3 terms  


DOI no: 10.1002/pro.5560041002 Protein Sci 4:1966-1976 (1995)
PubMed id: 8535233  
Stromelysin-1: three-dimensional structure of the inhibited catalytic domain and of the C-truncated proenzyme.
J.W.Becker, A.I.Marcy, L.L.Rokosz, M.G.Axel, J.J.Burbaum, P.M.Fitzgerald, P.M.Cameron, C.K.Esser, W.K.Hagmann, J.D.Hermes.
The proteolytic enzyme stromelysin-1 is a member of the family of matrix metalloproteinases and is believed to play a role in pathological conditions such as arthritis and tumor invasion. Stromelysin-1 is synthesized as a pro-enzyme that is activated by removal of an N-terminal prodomain. The active enzyme contains a catalytic domain and a C-terminal hemopexin domain believed to participate in macromolecular substrate recognition. We have determined the three-dimensional structures of both a C-truncated form of the proenzyme and an inhibited complex of the catalytic domain by X-ray diffraction analysis. The catalytic core is very similar in the two forms and is similar to the homologous domain in fibroblast and neutrophil collagenases, as well as to the stromelysin structure determined by NMR. The prodomain is a separate folding unit containing three alpha-helices and an extended peptide that lies in the active site of the enzyme. Surprisingly, the amino-to-carboxyl direction of this peptide chain is opposite to that adopted by the inhibitor and by previously reported inhibitors of collagenase. Comparison of the active site of stromelysin with that of thermolysin reveals that most of the residues proposed to play significant roles in the enzymatic mechanism of thermolysin have equivalents in stromelysin, but that three residues implicated in the catalytic mechanism of thermolysin are not represented in stromelysin.
  Selected figure(s)  
Figure 6.
Fig. 6. Hydrogenbondsinthestromelysinactivesite. A: he complexwith I. ComparewithFigure 3A. B: Theproenzymepro- peptide.Compare with Figure 3B. : Interaction between humanfibroblastcollagenaseandahydroxylamineinhibitor(Spurlino et al., Similarinteraction,exceptthatinvolvingGlu2190,wereobservedinanotherinhibitedcomplex of human fibroblastcollagenase(Borkakotietal., 1994). Similarinteractionswereobservedinaninhibitedcomplexofhumanneutro- philcollagenase(Stamsetal., D: InteractionsbetweenhumanfibroblastcollagenaseandtheN-terminusofanadjacent moleculeinthecrystallattice(Lovejoyetal., 1994b). : nteractions between humanfibroblastcollagenaseandacarboxyalkyl amineinhibitor(Lovejoyet al., 1994a).
Figure 10.
Fig. 10. Thermolysin and stromelysin catalytic residues and mechanism. : Proposed mechanism for thermolysin (Matthews, 1988). B Analogous mechanism for by Three Tyr 157, His 231, and sn 112) elieved to par- ticipate in thermolysin-catalyzed proteolysis have no equivalents in stromelysin.
  The above figures are reprinted from an Open Access publication published by the Protein Society: Protein Sci (1995, 4, 1966-1976) copyright 1995.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21044079 E.M.Kim, and O.Hwang (2011).
Role of matrix metalloproteinase-3 in neurodegeneration.
  J Neurochem, 116, 22-32.  
21087456 G.Murphy, and H.Nagase (2011).
Localizing matrix metalloproteinase activities in the pericellular environment.
  FEBS J, 278, 2.  
19459623 X.Xu, M.Mikhailova, U.Ilangovan, Z.Chen, A.Yu, S.Pal, A.P.Hinck, and B.Steffensen (2009).
Nuclear magnetic resonance mapping and functional confirmation of the collagen binding sites of matrix metalloproteinase-2.
  Biochemistry, 48, 5822-5831.  
18619669 G.Murphy, and H.Nagase (2008).
Progress in matrix metalloproteinase research.
  Mol Aspects Med, 29, 290-308.  
17763953 H.P.Shin, J.I.Lee, J.H.Jung, S.V.Yim, H.J.Kim, J.M.Cha, J.B.Park, K.R.Joo, J.S.Hwang, and B.K.Jang (2008).
Matrix metalloproteinase (MMP)-3 polymorphism in patients with HBV related chronic liver disease.
  Dig Dis Sci, 53, 823-829.  
18958412 S.H.Li, G.Li, H.M.Huang, F.Xiong, C.M.Liu, and G.G.Tu (2008).
The synthesis and preliminary activity assay in vitro of peptide-like derivatives as APN inhibitors.
  Arch Pharm Res, 31, 1231-1239.  
17942699 L.A.Ridnour, A.N.Windhausen, J.S.Isenberg, N.Yeung, D.D.Thomas, M.P.Vitek, D.D.Roberts, and D.A.Wink (2007).
Nitric oxide regulates matrix metalloproteinase-9 activity by guanylyl-cyclase-dependent and -independent pathways.
  Proc Natl Acad Sci U S A, 104, 16898-16903.  
17525979 M.VanSaun, B.C.Humburg, M.G.Arnett, M.Pence, and M.J.Werle (2007).
Activation of Matrix Metalloproteinase-3 is altered at the frog neuromuscular junction following changes in synaptic activity.
  Dev Neurobiol, 67, 1488-1497.  
16622849 M.N.VanSaun, and L.M.Matrisian (2006).
Matrix metalloproteinases and cellular motility in development and disease.
  Birth Defects Res C Embryo Today, 78, 69-79.  
16890240 S.Iyer, R.Visse, H.Nagase, and K.R.Acharya (2006).
Crystal structure of an active form of human MMP-1.
  J Mol Biol, 362, 78-88.
PDB code: 2clt
16622847 T.Tousseyn, E.Jorissen, K.Reiss, and D.Hartmann (2006).
(Make) stick and cut loose--disintegrin metalloproteases in development and disease.
  Birth Defects Res C Embryo Today, 78, 24-46.  
15526325 M.Kontoyianni, G.S.Sokol, and L.M.McClellan (2005).
Evaluation of library ranking efficacy in virtual screening.
  J Comput Chem, 26, 11-22.  
12595739 A.L.Gall, M.Ruff, and D.Moras (2003).
The dual role of CHAPS in the crystallization of stromelysin-3 catalytic domain.
  Acta Crystallogr D Biol Crystallogr, 59, 603-606.  
12887053 W.Bode, and K.Maskos (2003).
Structural basis of the matrix metalloproteinases and their physiological inhibitors, the tissue inhibitors of metalloproteinases.
  Biol Chem, 384, 863-872.  
12209155 C.M.Overall, and C.López-Otín (2002).
Strategies for MMP inhibition in cancer: innovations for the post-trial era.
  Nat Rev Cancer, 2, 657-672.  
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
12355408 T.Suzuki, Y.Kuwabara, H.Iwata, M.Mitani, N.Shinoda, A.Sato, A.Mitsui, M.Sugiura, J.Kato, and Y.Fujii (2002).
Role of matrix metalloproteinase-9 in in vitro invasion of esophageal carcinoma cells.
  J Surg Oncol, 81, 80-86.  
11168424 B.Arza, M.De Maeyer, J.Félez, D.Collen, and H.R.Lijnen (2001).
Critical role of glutamic acid 202 in the enzymatic activity of stromelysin-1 (MMP-3).
  Eur J Biochem, 268, 826-831.  
11592410 F.Grams, H.Brandstetter, S.D'Alò, D.Geppert, H.W.Krell, H.Leinert, V.Livi, E.Menta, A.Oliva, G.Zimmermann, F.Gram, H.Brandstetter, S.D'Alò, D.Geppert, H.W.Krell, H.Leinert, E.Livi VMenta, A.Oliva, and G.Zimmermann (2001).
Pyrimidine-2,4,6-Triones: a new effective and selective class of matrix metalloproteinase inhibitors.
  Biol Chem, 382, 1277-1285.  
11248710 V.Knäuper, M.L.Patterson, F.X.Gomis-Rüth, B.Smith, A.Lyons, A.J.Docherty, and G.Murphy (2001).
The role of exon 5 in fibroblast collagenase (MMP-1) substrate specificity and inhibitor selectivity.
  Eur J Biochem, 268, 1888-1896.  
10824119 Coignac, G.Elson, Y.Delneste, G.Magistrelli, P.Jeannin, J.P.Aubry, O.Berthier, D.Schmitt, J.Y.Bonnefoy, and J.F.Gauchat (2000).
Cloning of MMP-26. A novel matrilysin-like proteinase.
  Eur J Biochem, 267, 3323-3329.  
10813818 C.Marie-Claire, G.Tiraboschi, E.Ruffet, N.Inguimbert, M.C.Fournie-Zaluski, and B.P.Roques (2000).
Exploration of the S(')(1) subsite of neprilysin: a joined molecular modeling and site-directed mutagenesis study.
  Proteins, 39, 365-371.  
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.  
  10422833 A.G.Pavlovsky, M.G.Williams, Q.Z.Ye, D.F.Ortwine, C.F.Purchase, A.D.White, V.Dhanaraj, B.D.Roth, L.L.Johnson, D.Hupe, C.Humblet, and T.L.Blundell (1999).
X-ray structure of human stromelysin catalytic domain complexed with nonpeptide inhibitors: implications for inhibitor selectivity.
  Protein Sci, 8, 1455-1462.
PDB codes: 1b8y 1caq 1ciz 1qia 1qic
10500110 A.R.Khan, N.Khazanovich-Bernstein, E.M.Bergmann, and M.N.James (1999).
Structural aspects of activation pathways of aspartic protease zymogens and viral 3C protease precursors.
  Proc Natl Acad Sci U S A, 96, 10968-10975.  
9888808 C.M.Holman, C.C.Kan, M.R.Gehring, and H.E.Van Wart (1999).
Role of His-224 in the anomalous pH dependence of human stromelysin-1.
  Biochemistry, 38, 677-681.  
10500112 C.P.Sommerhoff, W.Bode, P.J.Pereira, M.T.Stubbs, J.Stürzebecher, G.P.Piechottka, G.Matschiner, and A.Bergner (1999).
The structure of the human betaII-tryptase tetramer: fo(u)r better or worse.
  Proc Natl Acad Sci U S A, 96, 10984-10991.  
10026247 D.E.Brodersen, J.Nyborg, and M.Kjeldgaard (1999).
Zinc-binding site of an S100 protein revealed. Two crystal structures of Ca2+-bound human psoriasin (S100A7) in the Zn2+-loaded and Zn2+-free states.
  Biochemistry, 38, 1695-1704.
PDB codes: 2psr 3psr
10353819 F.J.Moy, P.K.Chanda, J.M.Chen, S.Cosmi, W.Edris, J.S.Skotnicki, J.Wilhelm, and R.Powers (1999).
NMR solution structure of the catalytic fragment of human fibroblast collagenase complexed with a sulfonamide derivative of a hydroxamic acid compound.
  Biochemistry, 38, 7085-7096.
PDB codes: 3ayk 4ayk
9930993 G.Galazka, L.J.Windsor, H.Birkedal-Hansen, and J.A.Engler (1999).
Spontaneous propeptide processing of mini-stromelysin-1 mutants blocked by APMA ((4-Aminophenyl)mercuric acetate).
  Biochemistry, 38, 1316-1322.  
10545322 K.Briknarová, A.Grishaev, L.Bányai, H.Tordai, L.Patthy, and M.Llinás (1999).
The second type II module from human matrix metalloproteinase 2: structure, function and dynamics.
  Structure, 7, 1235-1245.
PDB code: 1cxw
  9568890 A.R.Khan, and M.N.James (1998).
Molecular mechanisms for the conversion of zymogens to active proteolytic enzymes.
  Protein Sci, 7, 815-836.  
  9792098 B.C.Finzel, E.T.Baldwin, G.L.Bryant, G.F.Hess, J.W.Wilks, C.M.Trepod, J.E.Mott, V.P.Marshall, G.L.Petzold, R.A.Poorman, T.J.O'Sullivan, H.J.Schostarez, and M.A.Mitchell (1998).
Structural characterizations of nonpeptidic thiadiazole inhibitors of matrix metalloproteinases reveal the basis for stromelysin selectivity.
  Protein Sci, 7, 2118-2126.
PDB codes: 1usn 2usn
  9827994 B.J.Stockman, D.J.Waldon, J.A.Gates, T.A.Scahill, D.A.Kloosterman, S.A.Mizsak, E.J.Jacobsen, K.L.Belonga, M.A.Mitchell, B.Mao, J.D.Petke, L.Goodman, E.A.Powers, S.R.Ledbetter, P.S.Kaytes, G.Vogeli, V.P.Marshall, G.L.Petzold, and R.A.Poorman (1998).
Solution structures of stromelysin complexed to thiadiazole inhibitors.
  Protein Sci, 7, 2281-2286.
PDB code: 3usn
9853686 D.E.Epps, R.A.Poorman, G.L.Petzold, C.W.Stuchly, A.L.Laborde, and J.H.Van Drie (1998).
The constituent tryptophans and bisANS as fluorescent probes of the active site and of a secondary binding site of stromelysin-1 (MMP-3).
  J Protein Chem, 17, 699-712.  
9585535 F.Ugwu, B.Van Hoef, A.Bini, D.Collen, and H.R.Lijnen (1998).
Proteolytic cleavage of urokinase-type plasminogen activator by stromelysin-1 (MMP-3).
  Biochemistry, 37, 7231-7236.  
  9655333 H.Brandstetter, R.A.Engh, E.G.Von Roedern, L.Moroder, R.Huber, W.Bode, and F.Grams (1998).
Structure of malonic acid-based inhibitors bound to human neutrophil collagenase. A new binding mode explains apparently anomalous data.
  Protein Sci, 7, 1303-1309.
PDB codes: 1a85 1a86
  9524070 K.Suzuki, C.C.Kan, W.Hung, M.R.Gehring, K.Brew, and H.Nagase (1998).
Expression of human pro-matrix metalloproteinase 3 that lacks the N-terminal 34 residues in Escherichia coli: autoactivation and interaction with tissue inhibitor of metalloproteinase 1 (TIMP-1).
  Biol Chem, 379, 185-191.  
  9524060 M.T.Stubbs, M.Renatus, and W.Bode (1998).
An active zymogen: unravelling the mystery of tissue-type plasminogen activator.
  Biol Chem, 379, 95.  
9657677 S.Arumugam, C.L.Hemme, N.Yoshida, K.Suzuki, H.Nagase, M.Berjanskii, B.Wu, and S.R.Van Doren (1998).
TIMP-1 contact sites and perturbations of stromelysin 1 mapped by NMR and a paramagnetic surface probe.
  Biochemistry, 37, 9650-9657.  
9760240 Y.C.Li, X.Zhang, R.Melton, V.Ganu, and N.C.Gonnella (1998).
Solution structure of the catalytic domain of human stromelysin-1 complexed to a potent, nonpeptidic inhibitor.
  Biochemistry, 37, 14048-14056.
PDB code: 1bm6
  9461346 J.C.Müller, E.G.von Roedern, F.Grams, H.Nagase, and L.Moroder (1997).
Non-peptidic cysteine derivatives as inhibitors of matrix metalloproteinases.
  Biol Chem, 378, 1475-1480.  
9249047 M.Betz, P.Huxley, S.J.Davies, Y.Mushtaq, M.Pieper, H.Tschesche, W.Bode, and F.X.Gomis-Rüth (1997).
1.8-A crystal structure of the catalytic domain of human neutrophil collagenase (matrix metalloproteinase-8) complexed with a peptidomimetic hydroxamate primed-side inhibitor with a distinct selectivity profile.
  Eur J Biochem, 247, 356-363.
PDB code: 1kbc
9346290 V.Knäuper, B.Smith, C.López-Otin, and G.Murphy (1997).
Activation of progelatinase B (proMMP-9) by active collagenase-3 (MMP-13).
  Eur J Biochem, 248, 369-373.  
  9165062 W.Baumeister, Z.Cejka, M.Kania, and E.Seemüller (1997).
The proteasome: a macromolecular assembly designed to confine proteolysis to a nanocompartment.
  Biol Chem, 378, 121-130.  
8756473 A.R.Welch, C.M.Holman, M.Huber, M.C.Brenner, M.F.Browner, and H.E.Van Wart (1996).
Understanding the P1' specificity of the matrix metalloproteinases: effect of S1' pocket mutations in matrilysin and stromelysin-1.
  Biochemistry, 35, 10103-10109.  
8639603 D.R.Wetmore, and K.D.Hardman (1996).
Roles of the propeptide and metal ions in the folding and stability of the catalytic domain of stromelysin (matrix metalloproteinase 3).
  Biochemistry, 35, 6549-6558.  
8765610 H.Nagase, and G.B.Fields (1996).
Human matrix metalloproteinase specificity studies using collagen sequence-based synthetic peptides.
  Biopolymers, 40, 399-416.  
8610113 I.Botos, L.Scapozza, D.Zhang, L.A.Liotta, and E.F.Meyer (1996).
Batimastat, a potent matrix mealloproteinase inhibitor, exhibits an unexpected mode of binding.
  Proc Natl Acad Sci U S A, 93, 2749-2754.
PDB code: 1dth
8961947 J.Cha, M.V.Pedersen, and D.S.Auld (1996).
Metal and pH dependence of heptapeptide catalysis by human matrilysin.
  Biochemistry, 35, 15831-15838.  
8740363 M.Cygler, J.Sivaraman, P.Grochulski, R.Coulombe, A.C.Storer, and J.S.Mort (1996).
Structure of rat procathepsin B: model for inhibition of cysteine protease activity by the proregion.
  Structure, 4, 405-416.
PDB code: 1mir
  8896443 R.Coulombe, P.Grochulski, J.Sivaraman, R.Ménard, J.S.Mort, and M.Cygler (1996).
Structure of human procathepsin L reveals the molecular basis of inhibition by the prosegment.
  EMBO J, 15, 5492-5503.
PDB code: 1cjl
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.