PDBsum entry 3edh

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Hydrolase PDB id
Protein chain
201 a.a. *
DMS ×5
_ZN ×2
Waters ×410
* Residue conservation analysis
PDB id:
Name: Hydrolase
Title: Crystal structure of bone morphogenetic protein 1 protease domain in complex with partially bound dmso
Structure: Bone morphogenetic protein 1. Chain: a. Fragment: protease domain. Synonym: bmp-1, procollagen c-proteinase, pcp, mammalian tolloid protein, mtld. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: bmp1, pcolc. Expressed in: escherichia coli. Expression_system_taxid: 562.
1.25Å     R-factor:   0.142     R-free:   0.172
Authors: A.Mac Sweeney
Key ref:
A.Mac Sweeney et al. (2008). Structural basis for the substrate specificity of bone morphogenetic protein 1/tolloid-like metalloproteases. J Mol Biol, 384, 228-239. PubMed id: 18824173 DOI: 10.1016/j.jmb.2008.09.029
03-Sep-08     Release date:   16-Sep-08    
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Protein chain
Pfam   ArchSchema ?
P13497  (BMP1_HUMAN) -  Bone morphogenetic protein 1
986 a.a.
201 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.  - Procollagen C-endopeptidase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: Cleavage of the C-terminal propeptide at Ala-|-Asp in type I and II procollagens and at Arg-|-Asp in type III.
      Cofactor: Zn(2+)
 Gene Ontology (GO) functional annotation 
  GO annot!
  Biological process     proteolysis   1 term 
  Biochemical function     metallopeptidase activity     3 terms  


DOI no: 10.1016/j.jmb.2008.09.029 J Mol Biol 384:228-239 (2008)
PubMed id: 18824173  
Structural basis for the substrate specificity of bone morphogenetic protein 1/tolloid-like metalloproteases.
A.Mac Sweeney, S.Gil-Parrado, D.Vinzenz, A.Bernardi, A.Hein, U.Bodendorf, P.Erbel, C.Logel, B.Gerhartz.
Procollagen C-peptidase, also known as bone morphogenetic protein 1 (BMP-1), is a multidomain, zinc endopeptidase of the astacin M12A family. BMP-1 is the prototype of a small group of proteases that have key roles in extracellular matrix formation and morphogenesis. BMP-1, its splice form mTLD, and the related proteases TLL-1 and TLL-2 are considered as promising drug targets for the treatment of excessive fibrosis and muscle wasting. We report here the crystal structures of the protease domains of human BMP-1 and the closely related Tolloid-like protease 1 (TLL-1). The crystal structures reveal an unexpected conformation of a cysteine-rich loop within the active site, and suggest that a flap movement is required in order to allow substrate binding. On the basis of these substantial differences between the BMP-1 and astacin active sites, a structural basis for their differing substrate specificities is proposed.
  Selected figure(s)  
Figure 1.
Fig. 1. The domain structure of full-length BMP-1, showing the EGF-like and complement-Uegf-BMP-1 domains C-terminal to the protease domain.
Figure 6.
Fig. 6. Characterization of the interaction between BMP-1 and a hydroxamic acid-based inhibitor. (a) Superimposed ^15N/^1H HSQC spectra of 60 μM [^15N]BMP-1 (black) and [^15N]BMP-1 with 200 μM inhibitor (magenta). (b) The concentration of free inhibitor plotted against increasing amounts of BMP-1. The concentration dependence of the observed reduction in peak intensity indicates a 1:1 binding event.
  The above figures are reprinted by permission from Elsevier: J Mol Biol (2008, 384, 228-239) copyright 2008.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
20545624 C.C.Rider, and B.Mulloy (2010).
Bone morphogenetic protein and growth differentiation factor cytokine families and their protein antagonists.
  Biochem J, 429, 1.  
19951429 N.Feiner, G.Begemann, A.J.Renz, A.Meyer, and S.Kuraku (2009).
The origin of bmp16, a novel Bmp2/4 relative, retained in teleost fish genomes.
  BMC Evol Biol, 9, 277.  
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