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PDBsum entry 1kn6

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protein links
Hydrolase PDB id
1kn6
Jmol
Contents
Protein chain
73 a.a. *
* Residue conservation analysis
PDB id:
1kn6
Name: Hydrolase
Title: Solution structure of the mouse prohormone convertase 1 pro- domain
Structure: Prohormone convertase 1. Chain: a. Fragment: n-terminal pro-domain. Synonym: neuroendocrine convertase 1. Engineered: yes
Source: Mus musculus. House mouse. Organism_taxid: 10090. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.
NMR struc: 20 models
Authors: M.A.Tangrea,P.N.Bryan,N.Sari,J.Orban
Key ref:
M.A.Tangrea et al. (2002). Solution structure of the pro-hormone convertase 1 pro-domain from Mus musculus. J Mol Biol, 320, 801-812. PubMed id: 12095256 DOI: 10.1016/S0022-2836(02)00543-0
Date:
18-Dec-01     Release date:   17-Jul-02    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P63239  (NEC1_MOUSE) -  Neuroendocrine convertase 1
Seq:
Struc:
 
Seq:
Struc:
753 a.a.
73 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.3.4.21.93  - Proprotein convertase 1.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: Release of protein hormones, neuropeptides and renin from their precursors, generally by cleavage of -Lys-Arg-|- bonds.

 

 
DOI no: 10.1016/S0022-2836(02)00543-0 J Mol Biol 320:801-812 (2002)
PubMed id: 12095256  
 
 
Solution structure of the pro-hormone convertase 1 pro-domain from Mus musculus.
M.A.Tangrea, P.N.Bryan, N.Sari, J.Orban.
 
  ABSTRACT  
 
The solution structure of the mouse pro-hormone convertase (PC) 1 pro-domain was determined using heteronuclear NMR spectroscopy and is the first structure to be obtained for any of the domains in the convertase family. The ensemble of NMR-derived structures shows a well-ordered core consisting of a four-stranded antiparallel beta-sheet with two alpha-helices packed against one side of this sheet. Sequence homology suggests that the other eukaryotic PC pro-domains will have the same overall fold and most of the residues forming the hydrophobic core of PC1 are highly conserved within the PC family. However, some of the core residues are predicted by homology to be replaced by polar amino acid residues in other PC pro-domains and this may help to explain their marginal stability. Interestingly, the folding topology observed here is also seen for the pro-domain of bacterial subtilisin despite little or no sequence homology. Both the prokaryotic and eukaryotic structures have hydrophobic residues clustered on the solvent-accessible surface of their beta-sheets although the individual residue types differ. In the bacterial case this region is buried at the binding interface with the catalytic domain and, in the eukaryotic PC family, these surface residues are conserved. We therefore propose that the hydrophobic patch in the PC1 pro-domain is involved in the binding interface with its cognate catalytic domain in a similar manner to that seen for the bacterial system. The PC1 pro-domain structure also reveals potential mechanisms for the acid-induced dissociation of the complex between pro- and catalytic domains.
 
  Selected figure(s)  
 
Figure 1.
Figure 1. Schematic representation of domain organization in the mammalian pro-hormone convertase family and comparison with bacterial subtilisin BPN'.
Figure 4.
Figure 4. (a) View from the a1-helix side of the hydrophobic core for a representative structure from the ensemble. Side-chains in the hydrophobic core are labeled and shown in purple. (b) View from the a2-helix side of the protein.
 
  The above figures are reprinted by permission from Elsevier: J Mol Biol (2002, 320, 801-812) copyright 2002.  
  Figures were selected by the author.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
19352504 K.Gawlik, S.A.Shiryaev, W.Zhu, K.Motamedchaboki, R.Desjardins, R.Day, A.G.Remacle, B.Stec, and A.Y.Strongin (2009).
Autocatalytic activation of the furin zymogen requires removal of the emerging enzyme's N-terminus from the active site.
  PLoS ONE, 4, e5031.  
17435765 D.Cunningham, D.E.Danley, K.F.Geoghegan, M.C.Griffor, J.L.Hawkins, T.A.Subashi, A.H.Varghese, M.J.Ammirati, J.S.Culp, L.R.Hoth, M.N.Mansour, K.M.McGrath, A.P.Seddon, S.Shenolikar, K.J.Stutzman-Engwall, L.C.Warren, D.Xia, and X.Qiu (2007).
Structural and biophysical studies of PCSK9 and its mutants linked to familial hypercholesterolemia.
  Nat Struct Mol Biol, 14, 413-419.
PDB code: 2p4e
17502100 D.E.Piper, S.Jackson, Q.Liu, W.G.Romanow, S.Shetterly, S.T.Thibault, B.Shan, and N.P.Walker (2007).
The crystal structure of PCSK9: a regulator of plasma LDL-cholesterol.
  Structure, 15, 545-552.
PDB code: 2pmw
17477394 S.Bhattacharjya, P.Xu, P.Wang, M.J.Osborne, and F.Ni (2007).
Conformational analyses of a partially-folded bioactive prodomain of human furin.
  Biopolymers, 86, 329-344.  
16407210 N.Rabah, D.Gauthier, B.C.Wilkes, D.J.Gauthier, and C.Lazure (2006).
Single amino acid substitution in the PC1/3 propeptide can induce significant modifications of its inhibitory profile toward its cognate enzyme.
  J Biol Chem, 281, 7556-7567.  
16601116 S.F.Feliciangeli, L.Thomas, G.K.Scott, E.Subbian, C.H.Hung, S.S.Molloy, F.Jean, U.Shinde, and G.Thomas (2006).
Identification of a pH sensor in the furin propeptide that regulates enzyme activation.
  J Biol Chem, 281, 16108-16116.  
15925704 M.Fugère, and R.Day (2005).
Cutting back on pro-protein convertases: the latest approaches to pharmacological inhibition.
  Trends Pharmacol Sci, 26, 294-301.  
16322767 P.K.Harris, S.Yeoh, A.R.Dluzewski, R.A.O'Donnell, C.Withers-Martinez, F.Hackett, L.H.Bannister, G.H.Mitchell, and M.J.Blackman (2005).
Molecular identification of a malaria merozoite surface sheddase.
  PLoS Pathog, 1, 241-251.  
15966813 M.A.Tangrea, B.S.Wallis, J.W.Gillespie, G.Gannot, M.R.Emmert-Buck, and R.F.Chuaqui (2004).
Novel proteomic approaches for tissue analysis.
  Expert Rev Proteomics, 1, 185-192.  
14528262 C.Brenner (2003).
Subtleties among subtilases. The structural biology of Kex2 and furin-related prohormone convertases.
  EMBO Rep, 4, 937-938.  
12721373 K.Ueda, G.M.Lipkind, A.Zhou, X.Zhu, A.Kuznetsov, L.Philipson, P.Gardner, C.Zhang, and D.F.Steiner (2003).
Mutational analysis of predicted interactions between the catalytic and P domains of prohormone convertase 3 (PC3/PC1).
  Proc Natl Acad Sci U S A, 100, 5622-5627.  
12414802 N.Nour, A.Basak, M.Chrétien, and N.G.Seidah (2003).
Structure-function analysis of the prosegment of the proprotein convertase PC5A.
  J Biol Chem, 278, 2886-2895.  
12794637 S.Henrich, A.Cameron, G.P.Bourenkov, R.Kiefersauer, R.Huber, I.Lindberg, W.Bode, and M.E.Than (2003).
The crystal structure of the proprotein processing proteinase furin explains its stringent specificity.
  Nat Struct Biol, 10, 520-526.
PDB code: 1p8j
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.