PDBsum entry 1eub

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Hydrolase/hydrolase inhibitor PDB id
Protein chain
171 a.a. *
_ZN ×2
_CA ×2
* Residue conservation analysis
PDB id:
Name: Hydrolase/hydrolase inhibitor
Title: Solution structure of the catalytic domain of human collagenase-3 (mmp-13) complexed to a potent non-peptidic sulfonamide inhibitor
Structure: Collagenase 3. Chain: a. Fragment: catalytic domain. Synonym: matrix metalloproteinase-13, mmp-13. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 562.
NMR struc: 20 models
Authors: X.Zhang,N.C.Gonnella,J.Koehn,N.Pathak,V.Ganu,R.Melton, D.Parker,S.I.Hu,K.Y.Nam
Key ref:
X.Zhang et al. (2000). Solution structure of the catalytic domain of human collagenase-3 (MMP-13) complexed to a potent non-peptidic sulfonamide inhibitor: binding comparison with stromelysin-1 and collagenase-1. J Mol Biol, 301, 513-524. PubMed id: 10926524 DOI: 10.1006/jmbi.2000.3988
14-Apr-00     Release date:   14-Apr-01    
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Protein chain
Pfam   ArchSchema ?
P45452  (MMP13_HUMAN) -  Collagenase 3
471 a.a.
171 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.2000.3988 J Mol Biol 301:513-524 (2000)
PubMed id: 10926524  
Solution structure of the catalytic domain of human collagenase-3 (MMP-13) complexed to a potent non-peptidic sulfonamide inhibitor: binding comparison with stromelysin-1 and collagenase-1.
X.Zhang, N.C.Gonnella, J.Koehn, N.Pathak, V.Ganu, R.Melton, D.Parker, S.I.Hu, K.Y.Nam.
The full three-dimensional structure of the catalytic domain of human collagenase-3 (MMP-13) complexed to a potent, sulfonamide hydroxamic acid inhibitor (CGS 27023) has been determined by NMR spectroscopy. The results reveal a core domain for the protein consisting of three alpha-helices and five beta-sheet strands with an overall tertiary fold similar to the catalytic domains of other matrix metalloproteinase family members. The S1' pocket, which is the major site of hydrophobic binding interaction, was found to be a wide cleft spanning the length of the protein and presenting facile opportunity for inhibitor extension deep into the pocket. Comparison with the reported X-ray structure of collagenase-3 showed evidence of flexibility for the loop region flanking the S1' pocket in both NMR and X-ray data. This flexibility was corroborated by NMR dynamics studies. Inhibitor binding placed the methoxy phenyl ring in the S1' pocket with the remainder of the molecule primarily solvent-exposed. The binding mode for this inhibitor was found to be similar with respect to stromelysin-1 and collagenase-1; however, subtle comparative differences in the interactions between inhibitor and enzyme were observed for the three MMPs that were consistent with their respective binding potencies.
  Selected figure(s)  
Figure 3.
Figure 3. Full 3D structure of the catalytic domain of human collagenase-3 complexed to CGS 27023. The enzyme backbone is shown in blue, antiparallel strand b4 in yellow and the inhibitor is shown in red. Zinc and calcium atoms appear as purple and gray spheres, respectively. Bi-dentate coordination with the catalytic zinc and hydrogen bonding interactions between the inhibitor's sulfonamide oxygen atoms and Leu185 [HN] and the inhibitor's 1HN and the carbonyl oxygen atom of Ala186 are displayed as white dotted lines. The relative orientation of S1' (extending into the plane of the page), S2' and S (opposite direction to S1') are displayed. The phenyl ring (pink) from Tyr214 forms a favorable perpendicular interaction with methoxy phenyl ring of the inhibitor.
Figure 5.
Figure 5. Active site of the collagenase-3-CGS 27023 complex. The inhibitor is displayed as a liquorice model. The NOEs defining the eclipsed orientation of the inhibitor's isopropyl group with its pyridine ring are shown as yellow dotted lines. The enzyme solid surface, generated with the GRASP program [Nicholls et al 1991], shows positive and negative charged surfaces as blue and red patches, respectively.
  The above figures are reprinted by permission from Elsevier: J Mol Biol (2000, 301, 513-524) 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, 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.  
17623656 A.R.Johnson, A.G.Pavlovsky, D.F.Ortwine, F.Prior, C.F.Man, D.A.Bornemeier, C.A.Banotai, W.T.Mueller, P.McConnell, C.Yan, V.Baragi, C.Lesch, W.H.Roark, M.Wilson, K.Datta, R.Guzman, H.K.Han, and R.D.Dyer (2007).
Discovery and characterization of a novel inhibitor of matrix metalloprotease-13 that reduces cartilage damage in vivo without joint fibroplasia side effects.
  J Biol Chem, 282, 27781-27791.
PDB codes: 2ow9 2ozr
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
15601584 I.Svab, D.Alexandru, G.Vitos, and M.L.Flonta (2004).
Binding affinities for sulfonamide inhibitors with matrix metalloproteinase-2 using a linear response method.
  J Cell Mol Med, 8, 551-562.  
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.