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PDBsum entry 1umt

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protein ligands metals links
Hydrolase/hydrolase inhibitor PDB id
1umt
Jmol
Contents
Protein chain
166 a.a. *
Ligands
0DS
Metals
_ZN ×2
_CA
* Residue conservation analysis
PDB id:
1umt
Name: Hydrolase/hydrolase inhibitor
Title: Stromelysin-1 catalytic domain with hydrophobic inhibitor bo 7.0, 32oc, 20 mm cacl2, 15% acetonitrile; nmr average of 20 structures minimized with restraints
Structure: Stromelysin-1. Chain: a. Fragment: catalytic domain residues 83 - 256. Synonym: matrix metalloproteinase-3, mmp-3. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: human stromelysin-1 catalytic. Expressed in: escherichia coli. Expression_system_taxid: 562. Other_details: induction by m13 with t7 RNA polymerase
NMR struc: 1 models
Authors: S.R.Van Doren,A.V.Kurochkin,W.Hu,E.R.P.Zuiderweg
Key ref: S.R.Van Doren et al. (1995). Solution structure of the catalytic domain of human stromelysin complexed with a hydrophobic inhibitor. Protein Sci, 4, 2487-2498. PubMed id: 8580839 DOI: 10.1002/pro.5560041205
Date:
31-Oct-95     Release date:   08-Mar-96    
PROCHECK
Go to PROCHECK summary
 Headers
 References

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

 Enzyme reactions 
   Enzyme class: E.C.3.4.24.17  - 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.5560041205 Protein Sci 4:2487-2498 (1995)
PubMed id: 8580839  
 
 
Solution structure of the catalytic domain of human stromelysin complexed with a hydrophobic inhibitor.
S.R.Van Doren, A.V.Kurochkin, W.Hu, Q.Z.Ye, L.L.Johnson, D.J.Hupe, E.R.Zuiderweg.
 
  ABSTRACT  
 
Stromelysin, a representative matrix metalloproteinase and target of drug development efforts, plays a prominent role in the pathological proteolysis associated with arthritis and secondarily in that of cancer metastasis and invasion. To provide a structural template to aid the development of therapeutic inhibitors, we have determined a medium-resolution structure of a 20-kDa complex of human stromelysin's catalytic domain with a hydrophobic peptidic inhibitor using multinuclear, multidimensional NMR spectroscopy. This domain of this zinc hydrolase contains a mixed beta-sheet comprising one antiparallel strand and four parallel strands, three helices, and a methionine-containing turn near the catalytic center. The ensemble of 20 structures was calculated using, on average, 8 interresidue NOE restraints per residue for the 166-residue protein fragment complexed with a 4-residue substrate analogue. The mean RMS deviation (RMSD) to the average structure for backbone heavy atoms is 0.91 A and for all heavy atoms is 1.42 A. The structure has good stereochemical properties, including its backbone torsion angles. The beta-sheet and alpha-helices of the catalytic domains of human stromelysin (NMR model) and human fibroblast collagenase (X-ray crystallographic model of Lovejoy B et al., 1994b, Biochemistry 33:8207-8217) superimpose well, having a pairwise RMSD for backbone heavy atoms of 2.28 A when three loop segments are disregarded. The hydroxamate-substituted inhibitor binds across the hydrophobic active site of stromelysin in an extended conformation. The first hydrophobic side chain is deeply buried in the principal S'1 subsite, the second hydrophobic side chain is located on the opposite side of the inhibitor backbone in the hydrophobic S'2 surface subsite, and a third hydrophobic side chain (P'3) lies at the surface.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
17710450 L.A.Alcaraz, L.Banci, I.Bertini, F.Cantini, A.Donaire, and L.Gonnelli (2007).
Matrix metalloproteinase-inhibitor interaction: the solution structure of the catalytic domain of human matrix metalloproteinase-3 with different inhibitors.
  J Biol Inorg Chem, 12, 1197-1206.
PDB codes: 2jnp 2jt5 2jt6
15809432 I.Bertini, V.Calderone, M.Cosenza, M.Fragai, Y.M.Lee, C.Luchinat, S.Mangani, B.Terni, and P.Turano (2005).
Conformational variability of matrix metalloproteinases: beyond a single 3D structure.
  Proc Natl Acad Sci U S A, 102, 5334-5339.
PDB codes: 1rmz 1y93 1ycm 1z3j
  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
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
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.  
  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.  
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
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
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.  
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 codes are shown on the right.