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PDBsum entry 1fm1

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protein ligands metals links
Hydrolase PDB id
1fm1
Jmol
Contents
Protein chain
158 a.a. *
Ligands
WAY
Metals
_ZN ×2
_CA
* Residue conservation analysis
PDB id:
1fm1
Name: Hydrolase
Title: Solution structure of the catalytic fragment of human collagenase-3 (mmp-13) complexed with a hydroxamic acid inhibitor
Structure: Collagenase-3. Chain: a. Fragment: catalytic fragment. Synonym: mmp-13. Engineered: yes. Other_details: hydroxamic acid inhibitor complex
Source: Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 562.
NMR struc: 30 models
Authors: F.J.Moy,P.K.Chanda,J.M.Chen,S.Cosmi,W.Edris,J.I.Levin, R.Powers
Key ref:
F.J.Moy et al. (2000). High-resolution solution structure of the catalytic fragment of human collagenase-3 (MMP-13) complexed with a hydroxamic acid inhibitor. J Mol Biol, 302, 671-689. PubMed id: 10986126 DOI: 10.1006/jmbi.2000.4082
Date:
15-Aug-00     Release date:   15-Aug-01    
PROCHECK
Go to PROCHECK summary
 Headers
 References

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

 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     extracellular region   2 terms 
  Biological process     collagen catabolic process   2 terms 
  Biochemical function     metallopeptidase activity     3 terms  

 

 
DOI no: 10.1006/jmbi.2000.4082 J Mol Biol 302:671-689 (2000)
PubMed id: 10986126  
 
 
High-resolution solution structure of the catalytic fragment of human collagenase-3 (MMP-13) complexed with a hydroxamic acid inhibitor.
F.J.Moy, P.K.Chanda, J.M.Chen, S.Cosmi, W.Edris, J.I.Levin, R.Powers.
 
  ABSTRACT  
 
The high-resolution solution structure of the catalytic fragment of human collagenase-3 (MMP-13) complexed with a sulfonamide derivative of a hydroxamic acid compound (WAY-151693) has been determined by multidimensional heteronuclear NMR. A total of 30 structures were calculated for residues 7-164 by means of hybrid distance geometry-simulated annealing using a total of 3280 experimental NMR restraints. The atomic rms distribution about the mean coordinate positions for the 30 structures is 0.43(+/-0.05) A for the backbone atoms, 0.80(+/-0.09) A for all atoms, and 0.47(+/-0.04) A for all atoms excluding disordered side-chains. The overall structure of MMP-13 is composed of a beta-sheet consisting of five beta-strands in a mixed parallel and anti-parallel arrangement and three alpha-helices where its overall fold is consistent with previously solved MMP structures. A comparison of the NMR structure of MMP-13 with the published 1.6 A resolution X-ray structure indicates that the major differences between the structures is associated with loop dynamics and crystal-packing interactions. The side-chains of some active-site residues for the NMR and X-ray structures of MMP-13 adopt distinct conformations. This is attributed to the presence of unique inhibitors in the two structures that encounter distinct interactions with MMP-13. The major structural difference observed between the MMP-13 and MMP-1 NMR structures is the relative size and shape of the S1' pocket where this pocket is significantly longer for MMP-13, nearly reaching the surface of the protein. Additionally, MMP-1 and MMP-13 exhibit different dynamic properties for the active-site loop and the structural Zn-binding region. The inhibitor WAY-151693 is well defined in the MMP-13 active-site based on a total of 52 distance restraints. The binding motif of WAY-151693 in the MMP-13 complex is consistent with our previously reported MMP-1:CGS-27023A NMR structure and is similar to the MMP-13: RS-130830 X-ray structure.
 
  Selected figure(s)  
 
Figure 1.
Figure 1. Illustration of the sulfonamide derivative of the hydroxamic acid inhibitor (WAY-151693) with the corresponding proton labels.
Figure 2.
Figure 2. Cross-eyed stereoview of (a) the MMP-13 bound conformation of WAY-151693 and (b) the MMP-1 bound conformation of CGS-27023A.
 
  The above figures are reprinted by permission from Elsevier: J Mol Biol (2000, 302, 671-689) copyright 2000.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
  19882751 J.D.Durrant, C.A.de Oliveira, and J.A.McCammon (2010).
Including receptor flexibility and induced fit effects into the design of MMP-2 inhibitors.
  J Mol Recognit, 23, 173-182.  
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
16470849 K.Paw┼éowski, M.Lepistö, N.Meinander, U.Sivars, M.Varga, and E.Wieslander (2006).
Novel conserved hydrolase domain in the CLCA family of alleged calcium-activated chloride channels.
  Proteins, 63, 424-439.  
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
14732707 V.Lukacova, Y.Zhang, M.Mackov, P.Baricic, S.Raha, J.A.Calvo, and S.Balaz (2004).
Similarity of binding sites of human matrix metalloproteinases.
  J Biol Chem, 279, 14194-14200.  
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.