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PDBsum entry 1avx

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protein metals Protein-protein interface(s) links
Complex (proteinase/inhibitor) PDB id
1avx
Jmol
Contents
Protein chains
223 a.a. *
172 a.a. *
Metals
_CA
Waters ×121
* Residue conservation analysis
PDB id:
1avx
Name: Complex (proteinase/inhibitor)
Title: Complex porcine pancreatic trypsin/soybean trypsin inhibitor, tetragonal crystal form
Structure: Trypsin. Chain: a. Synonym: ppt. Trypsin inhibitor. Chain: b. Synonym: sti
Source: Sus scrofa. Pig. Organism_taxid: 9823. Organ: pancreas. Glycine max. Soybean. Organism_taxid: 3847. Organ: seed
Biol. unit: Dimer (from PQS)
Resolution:
1.90Å     R-factor:   0.216     R-free:   0.280
Authors: H.K.Song,S.W.Suh
Key ref:
H.K.Song and S.W.Suh (1998). Kunitz-type soybean trypsin inhibitor revisited: refined structure of its complex with porcine trypsin reveals an insight into the interaction between a homologous inhibitor from Erythrina caffra and tissue-type plasminogen activator. J Mol Biol, 275, 347-363. PubMed id: 9466914 DOI: 10.1006/jmbi.1997.1469
Date:
21-Sep-97     Release date:   28-Oct-98    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P00761  (TRYP_PIG) -  Trypsin
Seq:
Struc:
231 a.a.
223 a.a.
Protein chain
Pfam   ArchSchema ?
P01070  (ITRA_SOYBN) -  Trypsin inhibitor A
Seq:
Struc:
216 a.a.
172 a.a.
Key:    PfamA domain  PfamB domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: Chain A: E.C.3.4.21.4  - Trypsin.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: Preferential cleavage: Arg-|-Xaa, Lys-|-Xaa.
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     extracellular region   2 terms 
  Biological process     digestion   4 terms 
  Biochemical function     catalytic activity     9 terms  

 

 
DOI no: 10.1006/jmbi.1997.1469 J Mol Biol 275:347-363 (1998)
PubMed id: 9466914  
 
 
Kunitz-type soybean trypsin inhibitor revisited: refined structure of its complex with porcine trypsin reveals an insight into the interaction between a homologous inhibitor from Erythrina caffra and tissue-type plasminogen activator.
H.K.Song, S.W.Suh.
 
  ABSTRACT  
 
The Kunitz-type trypsin inhibitor from soybean (STI) consists of 181 amino acid residues with two disulfide bridges. Its crystal structures have been determined in complex with porcine pancreatic trypsin in two crystal forms (an orthorhombic form at 1.75 A resolution and a tetragonal form at 1.9 A) and in the free state at 2.3 A resolution. They have been refined to crystallographic R-values of 18.9%, 21.6% and 19.8%, respectively. The three models of STI reported here represent a significant improvement over the partial inhibitor structure in the complex, which was previously determined at a nominal resolution of 2.6 A by the multiple isomorphous replacement method. This study provides the first high-resolution picture of the complex between a Kunitz-type proteinase inhibitor with its cognate proteinase. Many of the external loops of STI show high B-factors, both in the free and the complexed states, except the reactive site loop whose B-factors are dramatically reduced upon complexation. The reactive site loop of STI adopts a canonical conformation similar to those in other substrate-like inhibitors. The P1 carbonyl group displays no out-of-plane displacement and thus retains a nominal trigonal planar geometry. Modeling studies on the complex between a homologous Kunitz-type trypsin inhibitor DE-3 from Erythrina caffra and the human tissue-type plasminogen activator reveal a new insight into the specific interactions which could play a crucial role in their binding.
 
  Selected figure(s)  
 
Figure 5.
Figure 5. Stereo diagram showing the interactions between the bound water molecule (Wat34) and three β-strands (Aβ3, Bβ3 and Cβ3). The distances between the water and oxygen atoms of the inhibitor are given, with a distance too long for a hydrogen bond in parenthesis.
Figure 13.
Figure 13. A comparison of molecular surfaces. Positively charged regions are blue and negatively charged regions red. The P1 residue, S1 pocket and some basic and acidic patches are labeled. This figure was generated using GRASP (Nicholls, 1992).
 
  The above figures are reprinted by permission from Elsevier: J Mol Biol (1998, 275, 347-363) copyright 1998.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21354429 A.M.Ruvinsky, T.Kirys, A.V.Tuzikov, and I.A.Vakser (2011).
Side-chain conformational changes upon Protein-Protein Association.
  J Mol Biol, 408, 356-365.  
20931223 J.M.Mondego, M.P.Duarte, E.Kiyota, L.Martínez, S.R.de Camargo, F.P.De Caroli, B.S.Alves, S.M.Guerreiro, M.L.Oliva, O.Guerreiro-Filho, and M.Menossi (2011).
Molecular characterization of a miraculin-like gene differentially expressed during coffee development and coffee leaf miner infestation.
  Planta, 233, 123-137.  
20305655 B.G.Lee, E.Y.Park, K.E.Lee, H.Jeon, K.H.Sung, H.Paulsen, H.Rübsamen-Schaeff, H.Brötz-Oesterhelt, and H.K.Song (2010).
Structures of ClpP in complex with acyldepsipeptide antibiotics reveal its activation mechanism.
  Nat Struct Mol Biol, 17, 471-478.
PDB codes: 3ktg 3kth 3kti 3ktj 3ktk
20051032 M.Khalf, C.Goulet, J.Vorster, F.Brunelle, R.Anguenot, I.Fliss, and D.Michaud (2010).
Tubers from potato lines expressing a tomato Kunitz protease inhibitor are substantially equivalent to parental and transgenic controls.
  Plant Biotechnol J, 8, 155-169.  
19846555 M.Renko, J.Sabotic, M.Mihelic, J.Brzin, J.Kos, and D.Turk (2010).
Versatile loops in mycocypins inhibit three protease families.
  J Biol Chem, 285, 308-316.
PDB codes: 3h6q 3h6r 3h6s
20615447 P.Goettig, V.Magdolen, and H.Brandstetter (2010).
Natural and synthetic inhibitors of kallikrein-related peptidases (KLKs).
  Biochimie, 92, 1546-1567.  
  20073082 S.Khamrui, S.Majumder, J.Dasgupta, J.K.Dattagupta, and U.Sen (2010).
Identification of a novel set of scaffolding residues that are instrumental for the inhibitory property of Kunitz (STI) inhibitors.
  Protein Sci, 19, 593-602.
PDB codes: 3i2a 3i2x
19640842 R.Bao, C.Z.Zhou, C.Jiang, S.X.Lin, C.W.Chi, and Y.Chen (2009).
The ternary structure of the double-headed arrowhead protease inhibitor API-A complexed with two trypsins reveals a novel reactive site conformation.
  J Biol Chem, 284, 26676-26684.
PDB code: 3e8l
19780988 R.N.Philippe, S.G.Ralph, C.Külheim, S.I.Jancsik, and J.Bohlmann (2009).
Poplar defense against insects: genome analysis, full-length cDNA cloning, and transcriptome and protein analysis of the poplar Kunitz-type protease inhibitor family.
  New Phytol, 184, 865-884.  
19273853 S.Koutsopoulos, L.D.Unsworth, Y.Nagai, and S.Zhang (2009).
Controlled release of functional proteins through designer self-assembling peptide nanofiber hydrogel scaffold.
  Proc Natl Acad Sci U S A, 106, 4623-4628.  
  18997342 C.Jiang, R.Bao, and Y.Chen (2008).
Expression, purification, crystallization and preliminary X-ray diffraction analysis of Sagittaria sagittifolia arrowhead protease inhibitor API-A in complex with bovine trypsin.
  Acta Crystallogr Sect F Struct Biol Cryst Commun, 64, 1060-1062.  
17619961 T.Reiner, S.Kababya, and I.Gotman (2008).
Protein incorporation within Ti scaffold for bone ingrowth using Sol-gel SiO(2) as a slow release carrier.
  J Mater Sci Mater Med, 19, 583-589.  
17677103 I.A.Solov'yov, A.V.Yakubovich, A.V.Solov'yov, and W.Greiner (2007).
Two-center-multipole expansion method: application to macromolecular systems.
  Phys Rev E Stat Nonlin Soft Matter Phys, 75, 051912.  
16899489 A.D.van Dijk, and A.M.Bonvin (2006).
Solvated docking: introducing water into the modelling of biomolecular complexes.
  Bioinformatics, 22, 2340-2347.  
17027507 F.J.Milder, H.C.Raaijmakers, M.D.Vandeputte, A.Schouten, E.G.Huizinga, R.A.Romijn, W.Hemrika, A.Roos, M.R.Daha, and P.Gros (2006).
Structure of complement component C2A: implications for convertase formation and substrate binding.
  Structure, 14, 1587-1597.
PDB codes: 2i6q 2i6s
  17142906 M.Azarkan, A.Garcia-Pino, R.Dibiani, L.Wyns, R.Loris, and D.Baeyens-Volant (2006).
Crystallization and preliminary X-ray analysis of a protease inhibitor from the latex of Carica papaya.
  Acta Crystallogr Sect F Struct Biol Cryst Commun, 62, 1239-1242.  
16755353 N.M.Talyzina, and P.K.Ingvarsson (2006).
Molecular evolution of a small gene family of wound inducible Kunitz trypsin inhibitors in Populus.
  J Mol Evol, 63, 108-119.  
  17142903 Y.Hirano, M.M.Hossain, K.Takeda, H.Tokuda, and K.Miki (2006).
Purification, crystallization and preliminary X-ray crystallographic analysis of the outer membrane lipoprotein NlpE from Escherichia coli.
  Acta Crystallogr Sect F Struct Biol Cryst Commun, 62, 1227-1230.  
16214343 A.Gutteridge, and J.M.Thornton (2005).
Understanding nature's catalytic toolkit.
  Trends Biochem Sci, 30, 622-629.  
16085935 D.Navaneetham, L.Jin, P.Pandey, J.E.Strickler, R.E.Babine, S.S.Abdel-Meguid, and P.N.Walsh (2005).
Structural and mutational analyses of the molecular interactions between the catalytic domain of factor XIa and the Kunitz protease inhibitor domain of protease nexin 2.
  J Biol Chem, 280, 36165-36175.
PDB code: 1zjd
15778956 D.Segal, and M.Eisenstein (2005).
The effect of resolution-dependent global shape modifications on rigid-body protein-protein docking.
  Proteins, 59, 580-591.  
15665491 S.Iwanaga, N.Yamasaki, M.Kimura, and Y.Kouzuma (2005).
Contribution of conserved Asn residues to the inhibitory activities of Kunitz-type protease inhibitors from plants.
  Biosci Biotechnol Biochem, 69, 220-223.  
15632114 Z.Zhu, Z.Liang, T.Zhang, Z.Zhu, W.Xu, M.Teng, and L.Niu (2005).
Crystal structures and amidolytic activities of two glycosylated snake venom serine proteinases.
  J Biol Chem, 280, 10524-10529.
PDB codes: 1op0 1op2
15162493 A.Berchanski, B.Shapira, and M.Eisenstein (2004).
Hydrophobic complementarity in protein-protein docking.
  Proteins, 56, 130-142.  
14981658 A.R.Lopes, M.A.Juliano, L.Juliano, and W.R.Terra (2004).
Coevolution of insect trypsins and inhibitors.
  Arch Insect Biochem Physiol, 55, 140-152.  
15576329 I.Cruz-Silva, A.J.Gozzo, V.A.Nunes, A.K.Carmona, A.Faljoni-Alario, M.L.Oliva, M.U.Sampaio, C.A.Sampaio, and M.S.Araujo (2004).
A proteinase inhibitor from Caesalpinia echinata (pau-brasil) seeds for plasma kallikrein, plasmin and factor XIIa.
  Biol Chem, 385, 1083-1086.  
14747701 L.Prasad, Y.Leduc, K.Hayakawa, and L.T.Delbaere (2004).
The structure of a universally employed enzyme: V8 protease from Staphylococcus aureus.
  Acta Crystallogr D Biol Crystallogr, 60, 256-259.
PDB codes: 1qy6 2o8l
15606919 T.Z.Sen, A.Kloczkowski, R.L.Jernigan, C.Yan, V.Honavar, K.M.Ho, C.Z.Wang, Y.Ihm, H.Cao, X.Gu, and D.Dobbs (2004).
Predicting binding sites of hydrolase-inhibitor complexes by combining several methods.
  BMC Bioinformatics, 5, 205.  
12788916 I.H.Barrette-Ng, K.K.Ng, M.M.Cherney, G.Pearce, U.Ghani, C.A.Ryan, and M.N.James (2003).
Unbound form of tomato inhibitor-II reveals interdomain flexibility and conformational variability in the reactive site loops.
  J Biol Chem, 278, 31391-31400.
PDB code: 1pju
12931008 J.R.Bradford, and D.R.Westhead (2003).
Asymmetric mutation rates at enzyme-inhibitor interfaces: implications for the protein-protein docking problem.
  Protein Sci, 12, 2099-2103.  
12492470 M.Volpicella, L.R.Ceci, J.Cordewener, T.America, R.Gallerani, W.Bode, M.A.Jongsma, and J.Beekwilder (2003).
Properties of purified gut trypsin from Helicoverpa zea, adapted to proteinase inhibitors.
  Eur J Biochem, 270, 10-19.  
11847280 A.Heifetz, E.Katchalski-Katzir, and M.Eisenstein (2002).
Electrostatics in protein-protein docking.
  Protein Sci, 11, 571-587.  
12360523 O.L.Franco, M.F.Grossi de Sá, M.P.Sales, L.V.Mello, A.S.Oliveira, and D.J.Rigden (2002).
Overlapping binding sites for trypsin and papain on a Kunitz-type proteinase inhibitor from Prosopis juliflora.
  Proteins, 49, 335-341.  
11286627 C.Paine, E.Sharlow, F.Liebel, M.Eisinger, S.Shapiro, and M.Seiberg (2001).
An alternative approach to depigmentation by soybean extracts via inhibition of the PAR-2 pathway.
  J Invest Dermatol, 116, 587-595.  
11714927 S.R.Brych, S.I.Blaber, T.M.Logan, and M.Blaber (2001).
Structure and stability effects of mutations designed to increase the primary sequence symmetry within the core region of a beta-trefoil.
  Protein Sci, 10, 2587-2599.
PDB codes: 1jqz 1jt3 1jt4 1jt5 1jt7 1jtc
10328267 J.K.Dattagupta, A.Podder, C.Chakrabarti, U.Sen, D.Mukhopadhyay, S.K.Dutta, and M.Singh (1999).
Refined crystal structure (2.3 A) of a double-headed winged bean alpha-chymotrypsin inhibitor and location of its second reactive site.
  Proteins, 35, 321-331.
PDB code: 2wbc
10531477 S.Ravichandran, U.Sen, C.Chakrabarti, and J.K.Dattagupta (1999).
Cryocrystallography of a Kunitz-type serine protease inhibitor: the 90 K structure of winged bean chymotrypsin inhibitor (WCI) at 2.13 A resolution.
  Acta Crystallogr D Biol Crystallogr, 55, 1814-1821.
PDB code: 4wbc
9933620 T.Kishi, M.Kato, T.Shimizu, K.Kato, K.Matsumoto, S.Yoshida, S.Shiosaka, and T.Hakoshima (1999).
Crystal structure of neuropsin, a hippocampal protease involved in kindling epileptogenesis.
  J Biol Chem, 274, 4220-4224.
PDB code: 1npm
9915856 V.Y.Hook, C.Sei, S.Yasothornsrikul, T.Toneff, Y.H.Kang, S.Efthimiopoulos, N.K.Robakis, and W.Van Nostrand (1999).
The kunitz protease inhibitor form of the amyloid precursor protein (KPI/APP) inhibits the proneuropeptide processing enzyme prohormone thiol protease (PTP). Colocalization of KPI/APP and PTP in secretory vesicles.
  J Biol Chem, 274, 3165-3172.  
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.