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PDBsum entry 1mnc
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Hydrolase (metalloprotease) PDB id
1mnc

 

 

 

 

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Contents
Protein chain
158 a.a. *
Ligands
PLH
Metals
_ZN ×2
_CA
Waters ×72
* Residue conservation analysis
PDB id:
1mnc
Name: Hydrolase (metalloprotease)
Title: Structure of human neutrophil collagenase reveals large s1' specificity pocket
Structure: Neutrophil collagenase. Chain: a. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606
Resolution:
2.10Å     R-factor:   0.176    
Authors: T.Stams,J.C.Spurlino,D.L.Smith,B.Rubin
Key ref: T.Stams et al. (1994). Structure of human neutrophil collagenase reveals large S1' specificity pocket. Nat Struct Biol, 1, 119-123. PubMed id: 7656015
Date:
12-Jan-94     Release date:   07-Feb-95    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P22894  (MMP8_HUMAN) -  Neutrophil collagenase from Homo sapiens
Seq:
Struc: 		467 a.a.
158 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 3 residue positions (black crosses)

 Enzyme reactions 
   Enzyme class: E.C.3.4.24.34  - neutrophil collagenase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: Cleavage of interstitial collagens in the triple helical domain. Unlike EC 3.4.24.7, this enzyme cleaves type III collagen more slowly than type I.
      Cofactor: Ca(2+); Zn(2+)

 

 
Nat Struct Biol 1:119-123 (1994)
PubMed id: 7656015  
 
 
Structure of human neutrophil collagenase reveals large S1' specificity pocket.
T.Stams, J.C.Spurlino, D.L.Smith, R.C.Wahl, T.F.Ho, M.W.Qoronfleh, T.M.Banks, B.Rubin.
 
  ABSTRACT  
 
The crystal structure of the catalytic domain of human neutrophil collagenase complexed with a peptide transition state analogue has been determined to a resolution of 2.1 A. The structure of the neutrophil enzyme, when compared with the three dimensional structure of the corresponding human fibroblast collagenase, shows differences in the first, S1', of the three enzyme specificity subsites on the carboxy-terminal side of the substrate scissile bond. The S1' pocket in the neutrophil collagenase is significantly larger than the equivalent site in the fibroblast enzyme, suggesting that the former enzyme has a broader range of possible substrates. Such differences also suggest approaches for the design of selective matrix metalloproteinase inhibitors.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
18041759 B.Seebeck, I.Reulecke, A.Kämper, and M.Rarey (2008).
Modeling of metal interaction geometries for protein-ligand docking.
  Proteins, 71, 1237-1254.  
17050530 S.Iyer, S.Wei, K.Brew, and K.R.Acharya (2007).
Crystal structure of the catalytic domain of matrix metalloproteinase-1 in complex with the inhibitory domain of tissue inhibitor of metalloproteinase-1.
  J Biol Chem, 282, 364-371.
PDB code: 2j0t
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.  
14532275 H.I.Park, Y.Jin, D.R.Hurst, C.A.Monroe, S.Lee, M.A.Schwartz, and Q.X.Sang (2003).
The intermediate S1' pocket of the endometase/matrilysin-2 active site revealed by enzyme inhibition kinetic studies, protein sequence analyses, and homology modeling.
  J Biol Chem, 278, 51646-51653.  
12656997 V.J.Uitto, C.M.Overall, and C.McCulloch (2003).
Proteolytic host cell enzymes in gingival crevice fluid.
  Periodontol 2000, 31, 77.  
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.  
11967260 E.Llano, G.Adam, A.M.Pendás, V.Quesada, L.M.Sánchez, I.Santamariá, S.Noselli, and C.López-Otín (2002).
Structural and enzymatic characterization of Drosophila Dm2-MMP, a membrane-bound matrix metalloproteinase with tissue-specific expression.
  J Biol Chem, 277, 23321-23329.  
12228918 J.L.Lauer-Fields, D.Juska, and G.B.Fields (2002).
Matrix metalloproteinases and collagen catabolism.
  Biopolymers, 66, 19-32.  
12437092 J.L.Lauer-Fields, and G.B.Fields (2002).
Triple-helical peptide analysis of collagenolytic protease activity.
  Biol Chem, 383, 1095-1105.  
11939773 K.Kaur, K.Zhu, M.S.Whittemore, R.L.Petersen, A.Lichte, H.Tschesche, and T.Pourmotabbed (2002).
Identification of the active site of gelatinase B as the structural element sufficient for converting a protein to a metalloprotease.
  Biochemistry, 41, 4789-4797.  
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.  
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
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.  
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
10366106 G.N.Smith, E.A.Mickler, K.A.Hasty, and K.D.Brandt (1999).
Specificity of inhibition of matrix metalloproteinase activity by doxycycline: relationship to structure of the enzyme.
  Arthritis Rheum, 42, 1140-1146.  
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
10455161 L.L.Johnson, D.A.Bornemeier, J.A.Janowicz, J.Chen, A.G.Pavlovsky, and D.F.Ortwine (1999).
Effect of species differences on stromelysin-1 (MMP-3) inhibitor potency. An explanation of inhibitor selectivity using homology modeling and chimeric proteins.
  J Biol Chem, 274, 24881-24887.  
10187802 Q.Meng, V.Malinovskii, W.Huang, Y.Hu, L.Chung, H.Nagase, W.Bode, K.Maskos, and K.Brew (1999).
Residue 2 of TIMP-1 is a major determinant of affinity and specificity for matrix metalloproteinases but effects of substitutions do not correlate with those of the corresponding P1' residue of substrate.
  J Biol Chem, 274, 10184-10189.  
10194346 T.Meinnel, L.Patiny, S.Ragusa, and S.Blanquet (1999).
Design and synthesis of substrate analogue inhibitors of peptide deformylase.
  Biochemistry, 38, 4287-4295.  
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.  
9446583 A.Mucha, P.Cuniasse, R.Kannan, F.Beau, A.Yiotakis, P.Basset, and V.Dive (1998).
Membrane type-1 matrix metalloprotease and stromelysin-3 cleave more efficiently synthetic substrates containing unusual amino acids in their P1' positions.
  J Biol Chem, 273, 2763-2768.  
  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
9484219 F.J.Moy, P.K.Chanda, S.Cosmi, M.R.Pisano, C.Urbano, J.Wilhelm, and R.Powers (1998).
High-resolution solution structure of the inhibitor-free catalytic fragment of human fibroblast collagenase determined by multidimensional NMR.
  Biochemistry, 37, 1495-1504.
PDB codes: 1ayk 2ayk
  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
9437511 R.A.Greenwald, L.M.Golub, N.S.Ramamurthy, M.Chowdhury, S.A.Moak, and T.Sorsa (1998).
In vitro sensitivity of the three mammalian collagenases to tetracycline inhibition: relationship to bone and cartilage degradation.
  Bone, 22, 33-38.  
9484239 S.Parvathy, I.Hussain, E.H.Karran, A.J.Turner, and N.M.Hooper (1998).
Alzheimer's amyloid precursor protein alpha-secretase is inhibited by hydroxamic acid-based zinc metalloprotease inhibitors: similarities to the angiotensin converting enzyme secretase.
  Biochemistry, 37, 1680-1685.  
  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.  
9188724 K.Nomura, T.Shimizu, H.Kinoh, Y.Sendai, M.Inomata, and N.Suzuki (1997).
Sea urchin hatching enzyme (envelysin): cDNA cloning and deprivation of protein substrate specificity by autolytic degradation.
  Biochemistry, 36, 7225-7238.  
8647077 B.Chevrier, H.D'Orchymont, C.Schalk, C.Tarnus, and D.Moras (1996).
The structure of the Aeromonas proteolytica aminopeptidase complexed with a hydroxamate inhibitor. Involvement in catalysis of Glu151 and two zinc ions of the co-catalytic unit.
  Eur J Biochem, 237, 393-398.
PDB code: 1igb
8879550 C.Tarnus, J.M.Rémy, and H.d'Orchymont (1996).
3-Amino-2-hydroxy-propionaldehyde and 3-amino-1-hydroxy-propan-2-one derivatives: new classes of aminopeptidase inhibitors.
  Bioorg Med Chem, 4, 1287-1297.  
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.  
8917445 R.A.Williamson, D.Natalia, C.K.Gee, G.Murphy, M.D.Carr, and R.B.Freedman (1996).
Chemically and conformationally authentic active domain of human tissue inhibitor of metalloproteinases-2 refolded from bacterial inclusion bodies.
  Eur J Biochem, 241, 476-483.  
8740360 V.Dhanaraj, Q.Z.Ye, L.L.Johnson, D.J.Hupe, D.F.Ortwine, J.B.Dunbar, J.R.Rubin, A.Pavlovsky, C.Humblet, and T.L.Blundell (1996).
X-ray structure of a hydroxamate inhibitor complex of stromelysin catalytic domain and its comparison with members of the zinc metalloproteinase superfamily.
  Structure, 4, 375-386.  
8576151 V.Knäuper, C.López-Otin, B.Smith, G.Knight, and G.Murphy (1996).
Biochemical characterization of human collagenase-3.
  J Biol Chem, 271, 1544-1550.  
8561847 D.Soler, T.Nomizu, W.E.Brown, Y.Shibata, and D.S.Auld (1995).
Matrilysin: expression, purification, and characterization.
  J Protein Chem, 14, 511-520.  
7737183 F.Grams, P.Reinemer, J.C.Powers, T.Kleine, M.Pieper, H.Tschesche, R.Huber, and W.Bode (1995).
X-ray structures of human neutrophil collagenase complexed with peptide hydroxamate and peptide thiol inhibitors. Implications for substrate binding and rational drug design.
  Eur J Biochem, 228, 830-841.
PDB codes: 1jao 1jaq
  8535233 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, and J.D.Hermes (1995).
Stromelysin-1: three-dimensional structure of the inhibited catalytic domain and of the C-truncated proenzyme.
  Protein Sci, 4, 1966-1976.
PDB codes: 1slm 1sln
  8580839 S.R.Van Doren, A.V.Kurochkin, W.Hu, Q.Z.Ye, L.L.Johnson, D.J.Hupe, and E.R.Zuiderweg (1995).
Solution structure of the catalytic domain of human stromelysin complexed with a hydrophobic inhibitor.
  Protein Sci, 4, 2487-2498.
PDB codes: 1ums 1umt
8561849 T.Pourmotabbed, J.A.Aelion, D.Tyrrell, K.A.Hasty, C.H.Bu, and C.L.Mainardi (1995).
Role of the conserved histidine and aspartic acid residues in activity and stabilization of human gelatinase B: an example of matrix metalloproteinases.
  J Protein Chem, 14, 527-535.  
  7663339 W.Stöcker, F.Grams, U.Baumann, P.Reinemer, F.X.Gomis-Rüth, D.B.McKay, and W.Bode (1995).
The metzincins--topological and sequential relations between the astacins, adamalysins, serralysins, and matrixins (collagenases) define a superfamily of zinc-peptidases.
  Protein Sci, 4, 823-840.  
7583637 W.Stöcker, and W.Bode (1995).
Structural features of a superfamily of zinc-endopeptidases: the metzincins.
  Curr Opin Struct Biol, 5, 383-390.  
7712290 P.M.Colman (1994).
Structure-based drug design.
  Curr Opin Struct Biol, 4, 868-874.  
7656018 T.L.Blundell (1994).
Metalloproteinase superfamilies and drug design.
  Nat Struct Biol, 1, 73-75.  
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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