spacer
spacer

PDBsum entry 1a16

Go to PDB code: 
protein ligands metals links
Hydrolase/hydrolase inhibitor PDB id
1a16
Jmol
Contents
Protein chain
439 a.a. *
Ligands
PRO-LEU
Metals
_MN ×2
Waters ×346
* Residue conservation analysis
PDB id:
1a16
Name: Hydrolase/hydrolase inhibitor
Title: Aminopeptidase p from e. Coli with the inhibitor pro-leu
Structure: Aminopeptidase p. Chain: a. Synonym: ampp. Ec: 3.4.11.9
Source: Escherichia coli. Organism_taxid: 562. Strain: an1459/ppl670. Cellular_location: cytoplasm
Biol. unit: Homo-Tetramer (from PDB file)
Resolution:
2.30Å     R-factor:   0.184     R-free:   0.226
Authors: M.C.Wilce,C.S.Bond,P.E.Lilley,N.E.Dixon,H.C.Freeman,J.M.Guss
Key ref:
M.C.Wilce et al. (1998). Structure and mechanism of a proline-specific aminopeptidase from Escherichia coli. Proc Natl Acad Sci U S A, 95, 3472-3477. PubMed id: 9520390 DOI: 10.1073/pnas.95.7.3472
Date:
22-Dec-97     Release date:   06-Apr-99    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P15034  (AMPP_ECOLI) -  Xaa-Pro aminopeptidase
Seq:
Struc:
441 a.a.
439 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: Cobalt cation or Mn(2+)
 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: 10.1073/pnas.95.7.3472 Proc Natl Acad Sci U S A 95:3472-3477 (1998)
PubMed id: 9520390  
 
 
Structure and mechanism of a proline-specific aminopeptidase from Escherichia coli.
M.C.Wilce, C.S.Bond, N.E.Dixon, H.C.Freeman, J.M.Guss, P.E.Lilley, J.A.Wilce.
 
  ABSTRACT  
 
The structure of the proline-specific aminopeptidase (EC 3.4.11.9) from Escherichia coli has been solved and refined for crystals of the native enzyme at a 2.0-A resolution, for a dipeptide-inhibited complex at 2.3-A resolution, and for a low-pH inactive form at 2.7-A resolution. The protein crystallizes as a tetramer, more correctly a dimer of dimers, at both high and low pH, consistent with observations from analytical ultracentrifuge studies that show that the protein is a tetramer under physiological conditions. The monomer folds into two domains. The active site, in the larger C-terminal domain, contains a dinuclear manganese center in which a bridging water molecule or hydroxide ion appears poised to act as the nucleophile in the attack on the scissile peptide bond of Xaa-Pro. The metal-binding residues are located in a single subunit, but the residues surrounding the active site are contributed by three subunits. The fold of the protein resembles that of creatine amidinohydrolase (creatinase, not a metalloenzyme). The C-terminal catalytic domain is also similar to the single-domain enzyme methionine aminopeptidase that has a dinuclear cobalt center.
 
  Selected figure(s)  
 
Figure 1.
Fig. 1. (a) Orthogonal views of the tetramer of AMPP. Chain A is cyan, chain B is blue, chain C is green, and chain D is red. Mn2+ ions in the dinuclear active site are enlarged magenta spheres. (b) Stereo C^ trace of AMPP. Residues are color ramped from blue at the N terminus to red at the C terminus.
Figure 2.
Fig. 2. (a) Stereo view of the catalytic site of AMPP for native crystals at pH 8.3. Residues are colored by atom type. (b) Stereo view of the catalytic site of AMPP for crystals at pH 8.3 showing omit difference electron density for the inhibitor Pro-Leu contoured at 4 . (c) Stereo view of the catalytic site of AMPP for crystals at pH 4.6 showing omit difference electron density for coordinated acetate ion contoured at 4 .
 
  Figures were selected by the author.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21190293 A.Srivastava, and A.K.Sau (2010).
Biochemical studies on Helicobacter pylori arginase: insight into the difference in activity compared to other arginases.
  IUBMB Life, 62, 906-915.  
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.  
19837041 F.N.Vögtle, S.Wortelkamp, R.P.Zahedi, D.Becker, C.Leidhold, K.Gevaert, J.Kellermann, W.Voos, A.Sickmann, N.Pfanner, and C.Meisinger (2009).
Global analysis of the mitochondrial N-proteome identifies a processing peptidase critical for protein stability.
  Cell, 139, 428-439.  
  20130794 J.Jeyakanthan, K.Takada, M.Sawano, K.Ogasahara, H.Mizutani, N.Kunishima, S.Yokoyama, and K.Yutani (2009).
Crystal Structural and Functional Analysis of the Putative Dipeptidase from Pyrococcus horikoshii OT3.
  J Biophys, 2009, 434038.  
18340504 A.Lupi, R.Tenni, A.Rossi, G.Cetta, and A.Forlino (2008).
Human prolidase and prolidase deficiency: an overview on the characterization of the enzyme involved in proline recycling and on the effects of its mutations.
  Amino Acids, 35, 739-752.  
17876832 B.Nocek, R.Mulligan, M.Bargassa, F.Collart, and A.Joachimiak (2008).
Crystal structure of aminopeptidase N from human pathogen Neisseria meningitidis.
  Proteins, 70, 273-279.
PDB code: 2gtq
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.  
19019076 S.Mitra, K.M.Job, L.Meng, B.Bennett, and R.C.Holz (2008).
Analyzing the catalytic role of Asp97 in the methionine aminopeptidase from Escherichia coli.
  FEBS J, 275, 6248-6259.  
18649306 Y.T.Hsu, C.Y.Su, H.C.Du, S.C.Jao, and W.S.Li (2008).
Evaluation of organophosphorus chemicals-degrading enzymes: a comparison of Escherichia coli and human cytosolic aminopeptidase P.
  Chem Biodivers, 5, 1401-1411.  
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.  
17476590 K.S.Hui (2007).
Brain-specific aminopeptidase: from enkephalinase to protector against neurodegeneration.
  Neurochem Res, 32, 2062-2071.  
16594965 B.K.Singh, and A.Walker (2006).
Microbial degradation of organophosphorus compounds.
  FEMS Microbiol Rev, 30, 428-471.  
16820970 H.L.Yang, R.S.Chen, W.Chen, and L.L.Lin (2006).
Identification of glutamate residues important for catalytic activity of Bacillus stearothermophilus leucine aminopeptidase II.
  Antonie Van Leeuwenhoek, 90, 195-199.  
16517635 H.S.Lee, Y.J.Kim, S.S.Bae, J.H.Jeon, J.K.Lim, B.C.Jeong, S.G.Kang, and J.H.Lee (2006).
Cloning, expression, and characterization of aminopeptidase P from the hyperthermophilic archaeon Thermococcus sp. strain NA1.
  Appl Environ Microbiol, 72, 1886-1890.  
16761197 H.S.Lee, Y.J.Kim, S.S.Bae, J.H.Jeon, J.K.Lim, B.C.Jeong, S.G.Kang, and J.H.Lee (2006).
Cloning, expression, and characterization of a methionyl aminopeptidase from a hyperthermophilic archaeon Thermococcus sp. NA1.
  Mar Biotechnol (NY), 8, 425-432.  
16533030 J.I.Kliegman, S.L.Griner, J.D.Helmann, R.G.Brennan, and A.Glasfeld (2006).
Structural basis for the metal-selective activation of the manganese transport regulator of Bacillus subtilis.
  Biochemistry, 45, 3493-3505.
PDB codes: 2ev0 2ev5 2ev6 2f5c 2f5d 2f5e 2f5f
16470765 L.F.Huang, B.Su, S.C.Jao, K.T.Liu, and W.S.Li (2006).
Aminopeptidase p mediated detoxification of organophosphonate analogues of sarin: mechanistic and stereochemical study at the phosphorus atom of the substrate.
  Chembiochem, 7, 506-514.  
15928987 G.Y.Hwang, L.Y.Kuo, M.R.Tsai, S.L.Yang, and L.L.Lin (2005).
Histidines 345 and 378 of Bacillus stearothermophilus leucine aminopeptidase II are essential for the catalytic activity of the enzyme.
  Antonie Van Leeuwenhoek, 87, 355-359.  
15939021 L.W.Yang, and I.Bahar (2005).
Coupling between catalytic site and collective dynamics: a requirement for mechanochemical activity of enzymes.
  Structure, 13, 893-904.  
16235215 R.Kappl, K.Ranguelova, B.Koch, C.Duboc, and J.Hüttermann (2005).
Multi-frequency high-field EPR studies on metal-substituted xylose isomerase.
  Magn Reson Chem, 43, S65-S73.  
15578241 V.M.D'souza, R.S.Brown, B.Bennett, and R.C.Holz (2005).
Characterization of the active site and insight into the binding mode of the anti-angiogenesis agent fumagillin to the manganese(II)-loaded methionyl aminopeptidase from Escherichia coli.
  J Biol Inorg Chem, 10, 41-50.  
15901689 Y.Zheng, R.J.Roberts, S.Kasif, and C.Guan (2005).
Characterization of two new aminopeptidases in Escherichia coli.
  J Bacteriol, 187, 3671-3677.  
14705018 I.Ivanov, and M.L.Klein (2004).
First principles computational study of the active site of arginase.
  Proteins, 54, 1-7.  
15388923 S.C.Graham, M.J.Maher, W.H.Simmons, H.C.Freeman, and J.M.Guss (2004).
Structure of Escherichia coli aminopeptidase P in complex with the inhibitor apstatin.
  Acta Crystallogr D Biol Crystallogr, 60, 1770-1779.
PDB code: 1n51
15388919 V.Reiland, R.Gilboa, A.Spungin-Bialik, D.Schomburg, Y.Shoham, S.Blumberg, and G.Shoham (2004).
Binding of inhibitory aromatic amino acids to Streptomyces griseus aminopeptidase.
  Acta Crystallogr D Biol Crystallogr, 60, 1738-1746.
PDB codes: 1tf8 1tf9 1tkf 1tkh 1tkj
15583392 V.Reiland, Y.Fundoiano-Hershcovitz, G.Golan, R.Gilboa, Y.Shoham, and G.Shoham (2004).
Preliminary crystallographic characterization of BSAP, an extracellular aminopeptidase from Bacillus subtilis.
  Acta Crystallogr D Biol Crystallogr, 60, 2371-2376.  
12847518 A.Glasfeld, E.Guedon, J.D.Helmann, and R.G.Brennan (2003).
Structure of the manganese-bound manganese transport regulator of Bacillus subtilis.
  Nat Struct Biol, 10, 652-657.
PDB codes: 1on1 1on2
12777807 S.C.Graham, M.Lee, H.C.Freeman, and J.M.Guss (2003).
An orthorhombic form of Escherichia coli aminopeptidase P at 2.4 A resolution.
  Acta Crystallogr D Biol Crystallogr, 59, 897-902.
PDB code: 1m35
14646116 S.E.Rangarajan, A.Tocilj, Y.Li, P.Iannuzzi, A.Matte, and M.Cygler (2003).
Molecules of Escherichia coli MobB assemble into densely packed hollow cylinders in a crystal lattice with 75% solvent content.
  Acta Crystallogr D Biol Crystallogr, 59, 2348-2352.
PDB code: 1p9n
12405829 B.Bennett, W.E.Antholine, V.M.D'souza, G.Chen, L.Ustinyuk, and R.C.Holz (2002).
Structurally distinct active sites in the copper(II)-substituted aminopeptidases from Aeromonas proteolytica and Escherichia coli.
  J Am Chem Soc, 124, 13025-13034.  
12136144 B.Padmanabhan, A.Paehler, and M.Horikoshi (2002).
Structure of creatine amidinohydrolase from Actinobacillus.
  Acta Crystallogr D Biol Crystallogr, 58, 1322-1328.
PDB code: 1kp0
12111749 C.T.Supuran, A.Scozzafava, and B.W.Clare (2002).
Bacterial protease inhibitors.
  Med Res Rev, 22, 329-372.  
11223522 K.Willingham, M.J.Maher, A.M.Grunden, M.Ghosh, M.W.Adams, H.C.Freeman, and J.M.Guss (2001).
Crystallization and characterization of the prolidase from Pyrococcus furiosus.
  Acta Crystallogr D Biol Crystallogr, 57, 428-430.  
11606206 V.Laurent, D.R.Brooks, D.Coates, and R.E.Isaac (2001).
Functional expression and characterization of the cytoplasmic aminopeptidase P of Caenorhabditis elegans.
  Eur J Biochem, 268, 5430-5438.  
11106490 G.S.Cottrell, N.M.Hooper, and A.J.Turner (2000).
Cloning, expression, and characterization of human cytosolic aminopeptidase P: a single manganese(II)-dependent enzyme.
  Biochemistry, 39, 15121-15128.  
11106491 G.S.Cottrell, R.J.Hyde, J.Lim, M.R.Parsons, N.M.Hooper, and A.J.Turner (2000).
Identification of critical residues in the active site of porcine membrane-bound aminopeptidase P.
  Biochemistry, 39, 15129-15135.  
10872443 D.W.Christianson, and J.D.Cox (1999).
Catalysis by metal-activated hydroxide in zinc and manganese metalloenzymes.
  Annu Rev Biochem, 68, 33-57.  
10103026 M.Kobayashi, and S.Shimizu (1999).
Cobalt proteins.
  Eur J Biochem, 261, 1-9.  
10368287 S.Benini, W.R.Rypniewski, K.S.Wilson, S.Miletti, S.Ciurli, and S.Mangani (1999).
A new proposal for urease mechanism based on the crystal structures of the native and inhibited enzyme from Bacillus pasteurii: why urea hydrolysis costs two nickels.
  Structure, 7, 205-216.
PDB code: 2ubp
10387007 W.T.Lowther, A.M.Orville, D.T.Madden, S.Lim, D.H.Rich, and B.W.Matthews (1999).
Escherichia coli methionine aminopeptidase: implications of crystallographic analyses of the native, mutant, and inhibited enzymes for the mechanism of catalysis.
  Biochemistry, 38, 7678-7688.
PDB codes: 2mat 3mat 4mat
10555963 W.T.Lowther, Y.Zhang, P.B.Sampson, J.F.Honek, and B.W.Matthews (1999).
Insights into the mechanism of Escherichia coli methionine aminopeptidase from the structural analysis of reaction products and phosphorus-based transition-state analogues.
  Biochemistry, 38, 14810-14819.
PDB codes: 1c21 1c22 1c23 1c24 1c27
9770455 W.T.Lowther, D.A.McMillen, A.M.Orville, and B.W.Matthews (1998).
The anti-angiogenic agent fumagillin covalently modifies a conserved active-site histidine in the Escherichia coli methionine aminopeptidase.
  Proc Natl Acad Sci U S A, 95, 12153-12157.  
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.