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PDBsum entry 2bn7

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protein ligands metals links
Hydrolase PDB id
2bn7
Jmol
Contents
Protein chain
440 a.a. *
Ligands
PRO-LEU
FLC
Metals
_ZN
_MN ×2
_MG
Waters ×286
* Residue conservation analysis
PDB id:
2bn7
Name: Hydrolase
Title: Mn substituted e. Coli aminopeptidase p in complex with product and zn
Structure: Xaa-pro aminopeptidase. Chain: a. Synonym: aminopeptidase p, x-pro aminopeptidase, amino- pep ii, app-ii, aminoacylproline aminopeptidase. Engineered: yes. Other_details: dipeptide product of aminopeptidase p (forme clevage of xaa-pro-leu tripeptide substrate)
Source: Escherichia coli. Organism_taxid: 562. Strain: an1459. Expressed in: escherichia coli. Expression_system_taxid: 562.
Biol. unit: Tetramer (from PDB file)
Resolution:
2.40Å     R-factor:   0.166     R-free:   0.187
Authors: S.C.Graham,C.S.Bond,H.C.Freeman,J.M.Guss
Key ref:
S.C.Graham et al. (2005). Structural and functional implications of metal ion selection in aminopeptidase P, a metalloprotease with a dinuclear metal center. Biochemistry, 44, 13820-13836. PubMed id: 16229471 DOI: 10.1021/bi0512849
Date:
22-Mar-05     Release date:   29-Sep-05    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P15034  (AMPP_ECOLI) -  Xaa-Pro aminopeptidase
Seq:
Struc:
441 a.a.
440 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.3.4.11.9  - Xaa-Pro aminopeptidase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: Release of any N-terminal amino acid, including proline, that is linked with proline, even from a dipeptide or tripeptide.
      Cofactor: Manganese or cobalt
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     cytoplasm   2 terms 
  Biological process     proteolysis   1 term 
  Biochemical function     protein binding     8 terms  

 

 
DOI no: 10.1021/bi0512849 Biochemistry 44:13820-13836 (2005)
PubMed id: 16229471  
 
 
Structural and functional implications of metal ion selection in aminopeptidase P, a metalloprotease with a dinuclear metal center.
S.C.Graham, C.S.Bond, H.C.Freeman, J.M.Guss.
 
  ABSTRACT  
 
The effect of metal substitution on the activity and structure of the aminopeptidase P (APPro) from Escherichia coli has been investigated. Measurements of activity in the presence of Mn2+, Mg2+, Zn2+, Na+, and Ca2+ show that significant activity is seen only in the Mn-bound form of the enzyme. The addition of Zn2+ to [MnMn(APPro)] is strongly inhibitory. Crystal structures of [MnMn(APPro)], [MgMg(APPro)], [ZnZn(APPro)], [ZnMg(APPro)], [Ca_(APPro)], [Na_(APPro)], and [apo(APPro)] were determined. The structures of [Ca_(APPro)] and [Na_(APPro)] have a single metal atom at their active site. Surprisingly, when a tripeptide substrate (ValProLeu) was soaked into [Na_(APPro)] crystals in the presence of 200 mM Mg2+, the structure had substrate, but no metal, bound at the active site. The structure of apo APPro complexed with ValProLeu shows that the N-terminal amino group of a substrate can be bound at the active site by carboxylate side chains that normally bind the second metal atom, providing a model for substrate binding in a single-metal active enzyme. Structures of [MnMn(APPro)] and [ZnZn(APPro)] complexes of ProLeu, a product inhibitor, in the presence of excess Zn reveal a third metal-binding site, formed by two conserved His residues and the dipeptide inhibitor. A Zn atom bound at such a site would stabilize product binding and enhance inhibition.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
21274957 G.Grasso, A.Pietropaolo, G.Spoto, G.Pappalardo, G.R.Tundo, C.Ciaccio, M.Coletta, and E.Rizzarelli (2011).
Copper(I) and Copper(II) Inhibit Aβ Peptides Proteolysis by Insulin-Degrading Enzyme Differently: Implications for Metallostasis Alteration in Alzheimer's Disease.
  Chemistry, 17, 2752-2762.  
20138056 B.P.Nocek, D.M.Gillner, Y.Fan, R.C.Holz, and A.Joachimiak (2010).
Structural basis for catalysis by the mono- and dimetalated forms of the dapE-encoded N-succinyl-L,L-diaminopimelic acid desuccinylase.
  J Mol Biol, 397, 617-626.
PDB codes: 3ic1 3isz
20179356 J.F.O'Toole, Y.Liu, E.E.Davis, C.J.Westlake, M.Attanasio, E.A.Otto, D.Seelow, G.Nurnberg, C.Becker, M.Nuutinen, M.Kärppä, J.Ignatius, J.Uusimaa, S.Pakanen, E.Jaakkola, L.P.van den Heuvel, H.Fehrenbach, R.Wiggins, M.Goyal, W.Zhou, M.T.Wolf, E.Wise, J.Helou, S.J.Allen, C.A.Murga-Zamalloa, S.Ashraf, M.Chaki, S.Heeringa, G.Chernin, B.E.Hoskins, H.Chaib, J.Gleeson, T.Kusakabe, T.Suzuki, R.E.Isaac, L.M.Quarmby, B.Tennant, H.Fujioka, H.Tuominen, I.Hassinen, H.Lohi, J.L.van Houten, A.Rotig, J.A.Sayer, B.Rolinski, P.Freisinger, S.M.Madhavan, M.Herzer, F.Madignier, H.Prokisch, P.Nurnberg, P.K.Jackson, P.Jackson, H.Khanna, N.Katsanis, and F.Hildebrandt (2010).
Individuals with mutations in XPNPEP3, which encodes a mitochondrial protein, develop a nephronophthisis-like nephropathy.
  J Clin Invest, 120, 791-802.  
20378650 M.Kirkwood, N.E.Le Brun, J.D.Todd, and A.W.Johnston (2010).
The dddP gene of Roseovarius nubinhibens encodes a novel lyase that cleaves dimethylsulfoniopropionate into acrylate plus dimethyl sulfide.
  Microbiology, 156, 1900-1906.  
19574214 D.Ragheb, K.Bompiani, S.Dalal, and M.Klemba (2009).
Evidence for catalytic roles for Plasmodium falciparum aminopeptidase P in the food vacuole and cytosol.
  J Biol Chem, 284, 24806-24815.  
18669631 S.C.Chai, W.L.Wang, and Q.Z.Ye (2008).
FE(II) Is the Native Cofactor for Escherichia coli Methionine Aminopeptidase.
  J Biol Chem, 283, 26879-26885.  
17714507 J.W.Liu, K.S.Hadler, G.Schenk, and D.Ollis (2007).
Using directed evolution to improve the solubility of the C-terminal domain of Escherichia coli aminopeptidase P. Implications for metal binding and protein stability.
  FEBS J, 274, 4742-4751.  
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.