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PDBsum entry 1zlh

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protein metals Protein-protein interface(s) links
Hydrolase/hydrolase inhibitor PDB id
1zlh
Jmol
Contents
Protein chains
301 a.a. *
74 a.a. *
Metals
_ZN ×5
Waters ×379
* Residue conservation analysis
PDB id:
1zlh
Name: Hydrolase/hydrolase inhibitor
Title: Crystal structure of the tick carboxypeptidase inhibitor in complex with bovine carboxypeptidase a
Structure: Carboxypeptidase a1. Chain: a. Synonym: carboxypeptidase a, cpa, metallocarboxypeptidase. Engineered: yes. Carboxypeptidase inhibitor. Chain: b. Synonym: inhibitor of a/b metallocarboxypeptidases. Engineered: yes
Source: Bos taurus. Cattle. Organism_taxid: 9913. Expressed in: pichia pastoris. Expression_system_taxid: 4922. Rhipicephalus bursa. Organism_taxid: 67831. Expressed in: escherichia coli bl21. Expression_system_taxid: 511693.
Biol. unit: Dimer (from PQS)
Resolution:
1.70Å     R-factor:   0.156     R-free:   0.185
Authors: J.L.Arolas,G.M.Popowicz,J.Lorenzo,C.P.Sommerhoff,R.Huber, F.X.Aviles,T.A.Holak
Key ref:
J.L.Arolas et al. (2005). The three-dimensional structures of tick carboxypeptidase inhibitor in complex with A/B carboxypeptidases reveal a novel double-headed binding mode. J Mol Biol, 350, 489-498. PubMed id: 15961103 DOI: 10.1016/j.jmb.2005.05.015
Date:
06-May-05     Release date:   05-Jul-05    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P00730  (CBPA1_BOVIN) -  Carboxypeptidase A1
Seq:
Struc:
419 a.a.
301 a.a.*
Protein chain
Pfam   ArchSchema ?
Q5EPH2  (TCI1_RHIBU) -  Carboxypeptidase inhibitor
Seq:
Struc:
97 a.a.
74 a.a.
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 2 residue positions (black crosses)

 Enzyme reactions 
   Enzyme class: Chain A: E.C.3.4.17.1  - Carboxypeptidase A.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: Peptidyl-L-amino acid + H2O = peptide + L-amino acid

+
=
+
      Cofactor: Zn(2+)
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     cellular_component   2 terms 
  Biological process     hemostasis   7 terms 
  Biochemical function     enzyme inhibitor activity     6 terms  

 

 
    Added reference    
 
 
DOI no: 10.1016/j.jmb.2005.05.015 J Mol Biol 350:489-498 (2005)
PubMed id: 15961103  
 
 
The three-dimensional structures of tick carboxypeptidase inhibitor in complex with A/B carboxypeptidases reveal a novel double-headed binding mode.
J.L.Arolas, G.M.Popowicz, J.Lorenzo, C.P.Sommerhoff, R.Huber, F.X.Aviles, T.A.Holak.
 
  ABSTRACT  
 
The tick carboxypeptidase inhibitor (TCI) is a proteinaceous inhibitor of metallo-carboxypeptidases present in the blood-sucking tick Rhipicephalus bursa. The three-dimensional crystal structures of recombinant TCI bound to bovine carboxypeptidase A and to human carboxypeptidase B have been determined and refined at 1.7 A and at 2.0 A resolution, respectively. TCI consists of two domains that are structurally similar despite the low degree of sequence homology. The domains, each consisting of a short alpha-helix followed by a small twisted antiparallel beta-sheet, show a high level of structural homology to proteins of the beta-defensin-fold family. TCI anchors to the surface of mammalian carboxypeptidases in a double-headed manner not previously seen for carboxypeptidase inhibitors: the last three carboxy-terminal amino acid residues interact with the active site of the enzyme in a way that mimics substrate binding, and the N-terminal domain binds to an exosite distinct from the active-site groove. The structures of these complexes should prove valuable in the applications of TCI as a thrombolytic drug and as a basis for the design of novel bivalent carboxypeptidase inhibitors.
 
  Selected figure(s)  
 
Figure 2.
Figure 2. Comparison of the TCI domains with members of the b-defensin-fold family. The domains of TCI (N-terminal in red and C-terminal in dark blue), crotamine (PDB code 1H5O; in dark orange) and b-defensin-2 (PDB code 1FD3, chain A; in green) are superimposed and are shown as ribbons. The N and C-terminal ends are labeled. Cysteine residues, which are paired in a 1-5, 2-4, 3-6 fashion in all molecules, are indicated in yellow.
Figure 3.
Figure 3. Structure of the TCI-CPA complex shown in a stereo ribbon representation. The helix (a1) and b-strands (b1-b3 and b1'-b3') of TCI are shown in red and light blue, respectively, and the disulfide bridges are indicated in yellow. The side-chains of the last C-terminal residues of TCI are colored in orange. The helices and b-strands of CPA are shown in dark blue and dark green, respectively, and the catalytic zinc atom is represented by a yellow sphere. The N and C termini of TCI and CPA are labeled.
 
  The above figures are reprinted by permission from Elsevier: J Mol Biol (2005, 350, 489-498) copyright 2005.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21481778 E.Karaca, and A.M.Bonvin (2011).
A multidomain flexible docking approach to deal with large conformational changes in the modeling of biomolecular complexes.
  Structure, 19, 555-565.  
20812859 J.L.Arolas, and S.Ventura (2011).
Protease inhibitors as models for the study of oxidative folding.
  Antioxid Redox Signal, 14, 97.  
19273185 I.M.Francischetti, A.Sa-Nunes, B.J.Mans, I.M.Santos, and J.M.Ribeiro (2009).
The role of saliva in tick feeding.
  Front Biosci, 14, 2051-2088.  
19179285 L.Sanglas, F.X.Aviles, R.Huber, F.X.Gomis-Rüth, and J.L.Arolas (2009).
Mammalian metallopeptidase inhibition at the defense barrier of Ascaris parasite.
  Proc Natl Acad Sci U S A, 106, 1743-1747.
PDB code: 3fju
19604312 Y.Saito, S.Konnai, S.Yamada, S.Imamura, H.Nishikado, T.Ito, M.Onuma, and K.Ohashi (2009).
Identification and characterization of antimicrobial peptide, defensin, in the taiga tick, Ixodes persulcatus.
  Insect Mol Biol, 18, 531-539.  
19416536 Z.Valnickova, M.Thaysen-Andersen, P.Højrup, T.Christensen, K.W.Sanggaard, T.Kristensen, and J.J.Enghild (2009).
Biochemical characterization of bovine plasma thrombin-activatable fibrinolysis inhibitor (TAFI).
  BMC Biochem, 10, 13.  
18640980 J.L.Arolas, D.Pantoja-Uceda, S.Ventura, F.J.Blanco, and F.X.Aviles (2008).
The NMR Structures of the Major Intermediates of the Two-domain Tick Carboxypeptidase Inhibitor Reveal Symmetry in Its Folding and Unfolding Pathways.
  J Biol Chem, 283, 27110-27120.
PDB codes: 2k2x 2k2y 2k2z
18722183 L.Sanglas, Z.Valnickova, J.L.Arolas, I.Pallarés, T.Guevara, M.Solà, T.Kristensen, J.J.Enghild, F.X.Aviles, and F.X.Gomis-Rüth (2008).
Structure of activated thrombin-activatable fibrinolysis inhibitor, a molecular link between coagulation and fibrinolysis.
  Mol Cell, 31, 598-606.
PDB code: 3d4u
17325752 A.Wortmann, T.Pimenova, S.Alves, and R.Zenobi (2007).
Investigation of the first shot phenomenon in MALDI mass spectrometry of protein complexes.
  Analyst, 132, 199-207.  
17407161 D.Fernández, J.Vendrell, F.X.Avilés, and J.Fernández-Recio (2007).
Structural and functional characterization of binding sites in metallocarboxypeptidases based on Optimal Docking Area analysis.
  Proteins, 68, 131-144.  
17175446 F.J.Alarcon-Chaidez, J.Sun, and S.K.Wikel (2007).
Transcriptome analysis of the salivary glands of Dermacentor andersoni Stiles (Acari: Ixodidae).
  Insect Biochem Mol Biol, 37, 48-71.  
16760476 J.L.Arolas, S.Bronsoms, S.Ventura, F.X.Aviles, and J.J.Calvete (2006).
Characterizing the tick carboxypeptidase inhibitor: molecular basis for its two-domain nature.
  J Biol Chem, 281, 22906-22916.  
16260742 A.Bayés, M.Comellas-Bigler, M.Rodríguez de la Vega, K.Maskos, W.Bode, F.X.Aviles, M.A.Jongsma, J.Beekwilder, and J.Vendrell (2005).
Structural basis of the resistance of an insect carboxypeptidase to plant protease inhibitors.
  Proc Natl Acad Sci U S A, 102, 16602-16607.
PDB code: 2c1c
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.