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PDBsum entry 2kai
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protein Protein-protein interface(s) links
Complex (proteinase-inhibitor) PDB id
2kai

 

 

 

 

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Contents
Protein chains
80 a.a. *
152 a.a. *
57 a.a. *
Waters ×10
* Residue conservation analysis
PDB id:
2kai
Name: Complex (proteinase-inhibitor)
Title: Refined 2.5 angstroms x-ray crystal structure of the complex formed by porcine kallikrein a and the bovine pancreatic trypsin inhibitor. Crystallization, patterson search, structure determination, refinement, structure and comparison with its components and with the bovine trypsin-pancreatic trypsin inhibitor complex
Structure: Kallikrein a. Chain: a. Engineered: yes. Kallikrein a. Chain: b. Engineered: yes. Bovine pancreatic trypsin inhibitor. Chain: i. Engineered: yes
Source: Sus scrofa. Pig. Organism_taxid: 9823. Organ: pancreas. Bos taurus. Cattle. Organism_taxid: 9913
Biol. unit: Trimer (from PQS)
Resolution:
2.50Å     R-factor:   0.224    
Authors: W.Bode,Z.Chen
Key ref:
Z.Chen and W.Bode (1983). Refined 2.5 A X-ray crystal structure of the complex formed by porcine kallikrein A and the bovine pancreatic trypsin inhibitor. Crystallization, Patterson search, structure determination, refinement, structure and comparison with its components and with the bovine trypsin-pancreatic trypsin inhibitor complex. J Mol Biol, 164, 283-311. PubMed id: 6188842 DOI: 10.1016/0022-2836(83)90078-5
Date:
21-May-84     Release date:   19-Jul-84    
PROCHECK
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 Headers
 References

Protein chain
Pfam   ArchSchema ?
P00752  (KLK_PIG) -  Glandular kallikrein from Sus scrofa
Seq:
Struc: 		246 a.a.
80 a.a.
Protein chain
Pfam   ArchSchema ?
P00752  (KLK_PIG) -  Glandular kallikrein from Sus scrofa
Seq:
Struc: 		246 a.a.
152 a.a.*
Protein chain
Pfam   ArchSchema ?
P00974  (BPT1_BOVIN) -  Pancreatic trypsin inhibitor from Bos taurus
Seq:
Struc: 		100 a.a.
57 a.a.
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 4 residue positions (black crosses)

 Enzyme reactions 
   Enzyme class: Chains A, B: E.C.3.4.21.35  - tissue kallikrein.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: Preferential cleavage of Arg-|-Xaa bonds in small molecule substrates. Highly selective action to release kallidin (lysyl-bradykinin) from kininogen involves hydrolysis of Met-|-Xaa or Leu-|-Xaa. The rat enzyme is unusual in liberating bradykinin directly from autologous kininogens by cleavage at two Arg-|-Xaa bonds.

 

 
DOI no: 10.1016/0022-2836(83)90078-5 J Mol Biol 164:283-311 (1983)
PubMed id: 6188842  
 
 
Refined 2.5 A X-ray crystal structure of the complex formed by porcine kallikrein A and the bovine pancreatic trypsin inhibitor. Crystallization, Patterson search, structure determination, refinement, structure and comparison with its components and with the bovine trypsin-pancreatic trypsin inhibitor complex.
Z.Chen, W.Bode.
 
  ABSTRACT  
 
No abstract given.

 
  Selected figure(s)  
 
Figure 1.
Frc. 1. Tetragonal kallikrein APPTI crystal of approximate diameter @5 . 		Figure 5.
FIG. 5. (a) Peptide segment of free kallikrein (solid connections) including residues 668 t,o 67ti suprimposed bg the equivalent residues (168 to 176) of the kallikrein comonent of the PTI-complex (double connections), (b) Hydrogen-bonding scheme for the kallikrein segment Leo663 to Asp674 in the kallikrein-PTI complex.
 
  The above figures are reprinted by permission from Elsevier: J Mol Biol (1983, 164, 283-311) copyright 1983.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
20615447 P.Goettig, V.Magdolen, and H.Brandstetter (2010).
Natural and synthetic inhibitors of kallikrein-related peptidases (KLKs).
  Biochimie, 92, 1546-1567.  
17729269 A.May, and M.Zacharias (2008).
Energy minimization in low-frequency normal modes to efficiently allow for global flexibility during systematic protein-protein docking.
  Proteins, 70, 794-809.  
18844446 A.R.Lima, F.M.Alves, P.F.Angelo, D.Andrade, S.I.Blaber, M.Blaber, L.Juliano, and M.A.Juliano (2008).
S(1)' and S(2)' subsite specificities of human plasma kallikrein and tissue kallikrein 1 for the hydrolysis of peptides derived from the bradykinin domain of human kininogen.
  Biol Chem, 389, 1487-1494.  
18627343 M.Debela, N.Beaufort, V.Magdolen, N.M.Schechter, C.S.Craik, M.Schmitt, W.Bode, and P.Goettig (2008).
Structures and specificity of the human kallikrein-related peptidases KLK 4, 5, 6, and 7.
  Biol Chem, 389, 623-632.  
18939984 S.Bougouffa, and J.Warwicker (2008).
Volume-based solvation models out-perform area-based models in combined studies of wild-type and mutated protein-protein interfaces.
  BMC Bioinformatics, 9, 448.  
17976015 C.A.Borgoño, J.A.Gavigan, J.Alves, B.Bowles, J.L.Harris, G.Sotiropoulou, and E.P.Diamandis (2007).
Defining the extended substrate specificity of kallikrein 1-related peptidases.
  Biol Chem, 388, 1215-1225.  
17890654 M.I.Hassan, V.Kumar, R.K.Somvanshi, S.Dey, T.P.Singh, and S.Yadav (2007).
Structure-guided design of peptidic ligand for human prostate specific antigen.
  J Pept Sci, 13, 849-855.  
16740631 M.Debela, V.Magdolen, N.Schechter, M.Valachova, F.Lottspeich, C.S.Craik, Y.Choe, W.Bode, and P.Goettig (2006).
Specificity profiling of seven human tissue kallikreins reveals individual subsite preferences.
  J Biol Chem, 281, 25678-25688.  
15651049 G.Laxmikanthan, S.I.Blaber, M.J.Bernett, I.A.Scarisbrick, M.A.Juliano, and M.Blaber (2005).
1.70 A X-ray structure of human apo kallikrein 1: structural changes upon peptide inhibitor/substrate binding.
  Proteins, 58, 802-814.
PDB code: 1spj
15322279 E.S.Henriques, N.Fonseca, and M.J.Ramos (2004).
On the modeling of snake venom serine proteinase interactions with benzamidine-based thrombin inhibitors.
  Protein Sci, 13, 2355-2369.  
12108552 D.C.Pimenta, R.L.Melo, G.Caliendo, V.Santagada, F.Fiorino, B.Severino, G.de Nucci, L.Juliano, and M.A.Juliano (2002).
Design of inhibitors for human tissue kallikrein using non-natural aromatic and basic amino acids.
  Biol Chem, 383, 853-857.  
11863437 M.C.Hsieh, and B.S.Cooperman (2002).
Inhibition of prostate-specific antigen (PSA) by alpha(1)-antichymotrypsin: salt-dependent activation mediated by a conformational change.
  Biochemistry, 41, 2990-2997.  
11468412 A.L.Carvalho, J.M.Dias, L.Sanz, A.Romero, J.J.Calvete, and M.J.Romão (2001).
Purification, crystallization and identification by X-ray analysis of a prostate kallikrein from horse seminal plasma.
  Acta Crystallogr D Biol Crystallogr, 57, 1180-1183.  
10737939 D.W.Ritchie, and G.J.Kemp (2000).
Protein docking using spherical polar Fourier correlations.
  Proteins, 39, 178-194.  
10707029 J.D.Szustakowski, and Z.Weng (2000).
Protein structure alignment using a genetic algorithm.
  Proteins, 38, 428-440.  
10328272 G.Moont, H.A.Gabb, and M.J.Sternberg (1999).
Use of pair potentials across protein interfaces in screening predicted docked complexes.
  Proteins, 35, 364-373.  
10091673 G.S.Garrett, S.J.McPhail, K.Tornheim, P.E.Correa, and J.M.McIver (1999).
Synthesis of potent and selective inhibitors of human plasma kallikrein.
  Bioorg Med Chem Lett, 9, 301-306.  
10102985 H.Czapinska, and J.Otlewski (1999).
Structural and energetic determinants of the S1-site specificity in serine proteases.
  Eur J Biochem, 260, 571-595.  
10368273 I.Usón, G.M.Sheldrick, E.de La Fortelle, G.Bricogne, S.Di Marco, J.P.Priestle, M.G.Grütter, and P.R.Mittl (1999).
The 1.2 A crystal structure of hirustasin reveals the intrinsic flexibility of a family of highly disulphide-bridged inhibitors.
  Structure, 7, 55-63.
PDB codes: 1bx7 1bx8
10467148 K.P.Hopfner, A.Lang, A.Karcher, K.Sichler, E.Kopetzki, H.Brandstetter, R.Huber, W.Bode, and R.A.Engh (1999).
Coagulation factor IXa: the relaxed conformation of Tyr99 blocks substrate binding.
  Structure, 7, 989-996.
PDB code: 1rfn
10195448 M.A.Juliano, F.Filira, M.Gobbo, R.Rocchi, E.Del Nery, and L.Juliano (1999).
Chromogenic and fluorogenic glycosylated and acetylglycosylated peptides as substrates for serine, thiol and aspartyl proteases.
  J Pept Res, 53, 109-119.  
9926284 H.S.Margolius (1998).
Tissue kallikreins structure, regulation, and participation in mammalian physiology and disease.
  Clin Rev Allergy Immunol, 16, 337-349.  
9351801 B.Bax, T.L.Blundell, J.Murray-Rust, and N.Q.McDonald (1997).
Structure of mouse 7S NGF: a complex of nerve growth factor with four binding proteins.
  Structure, 5, 1275-1285.
PDB code: 1sgf
9179777 C.Capasso, M.Rizzi, E.Menegatti, P.Ascenzi, and M.Bolognesi (1997).
Crystal structure of the bovine alpha-chymotrypsin:Kunitz inhibitor complex. An example of multiple protein:protein recognition sites.
  J Mol Recognit, 10, 26-35.
PDB code: 1mtn
  9232643 D.E.Timm (1997).
The crystal structure of the mouse glandular kallikrein-13 (prorenin converting enzyme).
  Protein Sci, 6, 1418-1425.
PDB code: 1ao5
9032072 P.R.Mittl, S.Di Marco, G.Fendrich, G.Pohlig, J.Heim, C.Sommerhoff, H.Fritz, J.P.Priestle, and M.G.Grütter (1997).
A new structural class of serine protease inhibitors revealed by the structure of the hirustasin-kallikrein complex.
  Structure, 5, 253-264.
PDB code: 1hia
9311976 R.Lapatto, U.Krengel, H.A.Schreuder, A.Arkema, B.de Boer, K.H.Kalk, W.G.Hol, P.D.Grootenhuis, J.W.Mulders, R.Dijkema, H.J.Theunissen, and B.W.Dijkstra (1997).
X-ray structure of antistasin at 1.9 A resolution and its modelled complex with blood coagulation factor Xa.
  EMBO J, 16, 5151-5161.
PDB code: 1skz
9254605 T.Kurth, D.Ullmann, H.D.Jakubke, and L.Hedstrom (1997).
Converting trypsin to chymotrypsin: structural determinants of S1' specificity.
  Biochemistry, 36, 10098-10104.  
8679538 B.F.Le Bonniec, T.Myles, T.Johnson, C.G.Knight, C.Tapparelli, and S.R.Stone (1996).
Characterization of the P2' and P3' specificities of thrombin using fluorescence-quenched substrates and mapping of the subsites by mutagenesis.
  Biochemistry, 35, 7114-7122.  
  8732755 B.O.Villoutreix, H.Lilja, K.Pettersson, T.Lövgren, and O.Teleman (1996).
Structural investigation of the alpha-1-antichymotrypsin: prostate-specific antigen complex by comparative model building.
  Protein Sci, 5, 836-851.  
8703913 J.A.Kraunsoe, T.D.Claridge, and G.Lowe (1996).
Inhibition of human leukocyte and porcine pancreatic elastase by homologues of bovine pancreatic trypsin inhibitor.
  Biochemistry, 35, 9090-9096.  
8702506 M.Matos, M.C.Fann, R.T.Yan, and P.C.Maloney (1996).
Enzymatic and biochemical probes of residues external to the translocation pathway of UhpT, the sugar phosphate carrier of Escherichia coli.
  J Biol Chem, 271, 18571-18575.  
  8528086 A.Wallqvist, R.L.Jernigan, and D.G.Covell (1995).
A preference-based free-energy parameterization of enzyme-inhibitor binding. Applications to HIV-1-protease inhibitor design.
  Protein Sci, 4, 1881-1903.  
7716167 J.Janin (1995).
Elusive affinities.
  Proteins, 21, 30-39.  
  7535613 B.O.Villoutreix, E.D.Getzoff, and J.H.Griffin (1994).
A structural model for the prostate disease marker, human prostate-specific antigen.
  Protein Sci, 3, 2033-2044.
PDB code: 1pfa
7909667 M.Fahnestock (1994).
Characterization of kallikrein cDNAs from the African rodent Mastomys.
  DNA Cell Biol, 13, 293-300.  
7527150 Q.Zheng, and D.J.Kyle (1994).
Multiple copy sampling: rigid versus flexible protein.
  Proteins, 19, 324-329.  
  7703837 R.A.Bradshaw, J.Murray-Rust, C.F.Ibáñez, N.Q.McDonald, R.Lapatto, and T.L.Blundell (1994).
Nerve growth factor: structure/function relationships.
  Protein Sci, 3, 1901-1913.  
7527234 R.Oddone, D.Barra, G.Amiconi, P.Ascenzi, C.Tarricone, M.Bolognesi, F.Bortolotti, and E.Menegatti (1994).
Binding of native and [homoserine lactone-52]-52,53-seco-bovine basic pancreatic trypsin inhibitor (Kunitz inhibitor) to porcine pancreatic beta-kallikrein-B and bovine alpha-chymotrypsin: thermodynamic study.
  J Mol Recognit, 7, 39-46.  
7803238 T.Miyata, K.Kuze, T.Matsusue, H.Komooka, K.Kamiya, H.Umeyama, A.Matsui, H.Kato, and A.Yoshioka (1994).
Factor IX Bm Kiryu: a Val-313-to-Asp substitution in the catalytic domain results in loss of function due to a conformational change of the surface loop: evidence obtained by chimaeric modelling.
  Br J Haematol, 88, 156-165.  
  8401208 B.Bax, M.Blaber, G.Ferguson, M.J.Sternberg, and P.H.Walls (1993).
Prediction of the three-dimensional structures of the nerve growth factor and epidermal growth factor binding proteins (kallikreins) and an hypothetical structure of the high molecular weight complex of epidermal growth factor with its binding protein.
  Protein Sci, 2, 1229-1241.  
8386628 B.Hinzmann, D.Wernicke, M.Pfeifer, U.Zacharias, B.Fischer, F.Eisenmenger, and H.Will (1993).
Tissue-type plasminogen activator mutants imitating urokinase in the peptide link between kringle and protease domains and at selected sites within the protease domain.
  Eur J Biochem, 213, 437-443.  
7685280 L.C.Petersen, J.J.Birktoft, and H.Flodgaard (1993).
Binding of bovine pancreatic trypsin inhibitor to heparin binding protein/CAP37/azurocidin. Interaction between a Kunitz-type inhibitor and a proteolytically inactive serine proteinase homologue.
  Eur J Biochem, 214, 271-279.  
  1304887 E.Meyer (1992).
Internal water molecules and H-bonding in biological macromolecules: a review of structural features with functional implications.
  Protein Sci, 1, 1543-1562.  
  1339024 N.Horton, and M.Lewis (1992).
Calculation of the free energy of association for protein complexes.
  Protein Sci, 1, 169-181.  
1472381 N.P.Burton, and C.R.Lowe (1992).
Design of novel affinity adsorbents for the purification of trypsin-like proteases.
  J Mol Recognit, 5, 55-68.  
1541261 W.Bode, and R.Huber (1992).
Natural protein proteinase inhibitors and their interaction with proteinases.
  Eur J Biochem, 204, 433-451.  
1584773 Y.Takeuchi, T.Nonaka, K.T.Nakamura, S.Kojima, K.Miura, and Y.Mitsui (1992).
Crystal structure of an engineered subtilisin inhibitor complexed with bovine trypsin.
  Proc Natl Acad Sci U S A, 89, 4407-4411.
PDB code: 2tld
1678522 B.F.Le Bonniec, and C.T.Esmon (1991).
Glu-192----Gln substitution in thrombin mimics the catalytic switch induced by thrombomodulin.
  Proc Natl Acad Sci U S A, 88, 7371-7375.  
2085383 O.Matsumoto, T.Taga, T.Higashi, M.Matsushima, and K.Machida (1990).
Complex formation by bovine trypsin and a tetrapeptide (Leu-Arg-Pro-Gly-NH2): X-ray structure analysis of the complex in the orthorhombic crystal form with low molecular packing density.
  J Protein Chem, 9, 589-593.  
2472912 B.J.Morris (1989).
hGK-1: a kallikrein gene expressed in human prostate.
  Clin Exp Pharmacol Physiol, 16, 345-351.  
2514275 M.J.Dufton, P.Bladon, and A.L.Harvey (1989).
Identification of a locality in snake venom alpha-neurotoxins with a significant compositional similarity to marine snail alpha-conotoxins: implications for evolution and structure/activity.
  J Mol Evol, 29, 355-366.  
2678630 T.E.Creighton, and N.J.Darby (1989).
Functional evolutionary divergence of proteolytic enzymes and their inhibitors.
  Trends Biochem Sci, 14, 319-324.  
3228244 L.B.Evnin, and C.S.Craik (1988).
Development of an efficient method for generating and screening active trypsin and trypsin variants.
  Ann N Y Acad Sci, 542, 61-74.  
3643848 F.Fiedler (1987).
Effects of secondary interactions on the kinetics of peptide and peptide ester hydrolysis by tissue kallikrein and trypsin.
  Eur J Biochem, 163, 303-312.  
3493250 P.J.Isackson, J.C.Dunbar, and R.A.Bradshaw (1987).
Role of glandular kallikreins as growth factor processing enzymes: structural and evolutionary considerations.
  J Cell Biochem, 33, 65-75.  
3301348 W.Bode, E.Papamokos, and D.Musil (1987).
The high-resolution X-ray crystal structure of the complex formed between subtilisin Carlsberg and eglin c, an elastase inhibitor from the leech Hirudo medicinalis. Structural analysis, subtilisin structure and interface geometry.
  Eur J Biochem, 166, 673-692.
PDB code: 1cse
3104578 E.Menegatti, M.Bolognesi, S.Scalia, F.Bortolotti, M.Guarneri, and P.Ascenzi (1986).
Gabexate mesylate inhibition of serine proteases: thermodynamic and computer-graphics analysis.
  J Pharm Sci, 75, 1171-1174.  
2432957 P.Ascenzi, G.Amiconi, M.Bolognesi, E.Menegatti, and M.Guarneri (1986).
Binding of porcine pancreatic secretory trypsin inhibitor to bovine beta-trypsin: a kinetic study.
  Biopolymers, 25, 2325-2333.  
  3640709 W.Bode, A.Z.Wei, R.Huber, E.Meyer, J.Travis, and S.Neumann (1986).
X-ray crystal structure of the complex of human leukocyte elastase (PMN elastase) and the third domain of the turkey ovomucoid inhibitor.
  EMBO J, 5, 2453-2458.
PDB code: 1ppf
2436242 A.L.Harvey, and A.J.Anderson (1985).
Dendrotoxins: snake toxins that block potassium channels and facilitate neurotransmitter release.
  Pharmacol Ther, 31, 33-55.  
4076193 M.J.Dufton (1985).
Proteinase inhibitors and dendrotoxins. Sequence classification, structural prediction and structure/activity.
  Eur J Biochem, 153, 647-654.  
6207021 W.Bode, J.Walter, R.Huber, H.R.Wenzel, and H.Tschesche (1984).
The refined 2.2-A (0.22-nm) X-ray crystal structure of the ternary complex formed by bovine trypsinogen, valine-valine and the Arg15 analogue of bovine pancreatic trypsin inhibitor.
  Eur J Biochem, 144, 185-190.
PDB code: 4tpi
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.

 

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