spacer
spacer

PDBsum entry 4tpi
Go to PDB code: 
protein ligands metals Protein-protein interface(s) links
Hydrolase/hydrolase inhibitor PDB id
4tpi

 

 

 

 

Loading ...

 
JSmol PyMol  
Contents
Protein chains
223 a.a. *
58 a.a. *
Ligands
VAL-VAL
SO4 ×2
Metals
_CA
Waters ×155
* Residue conservation analysis
PDB id:
4tpi
Name: Hydrolase/hydrolase inhibitor
Title: The refined 2.2-angstroms (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
Structure: Trypsinogen. Chain: z. Bovine pancreatic trypsin inhibitor. Chain: i. Engineered: yes
Source: Bos taurus. Cattle. Organism_taxid: 9913. Organ: pancreas.
Biol. unit: Dodecamer (from PQS)
Resolution:
2.20Å     R-factor:   0.170    
Authors: W.Bode,J.Walter
Key ref: W.Bode et al. (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. PubMed id: 6207021
Date:
11-Jun-85     Release date:   08-Nov-85    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P00760  (TRY1_BOVIN) -  Serine protease 1 from Bos taurus
Seq:
Struc: 		246 a.a.
223 a.a.
Protein chain
Pfam   ArchSchema ?
P00974  (BPT1_BOVIN) -  Pancreatic trypsin inhibitor from Bos taurus
Seq:
Struc: 		100 a.a.
58 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 1 residue position (black cross)

 Enzyme reactions 
   Enzyme class: Chain Z: E.C.3.4.21.4  - trypsin.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: Preferential cleavage: Arg-|-Xaa, Lys-|-Xaa.

 

 
Eur J Biochem 144:185-190 (1984)
PubMed id: 6207021  
 
 
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.
W.Bode, J.Walter, R.Huber, H.R.Wenzel, H.Tschesche.
 
  ABSTRACT  
 
Large orthorhombic crystals of the complex formed by bovine trypsinogen and a semisynthetic homologous bovine pancreatic trypsin inhibitor with the reactive-site lysine residue replaced by an arginine residue [( Arg15]PTI) have been obtained which are isomorphous with the crystals of PTI-trypsinogen [Bode, W., Schwager, P. and Huber, R. (1978) J. Mol. Biol. 118, 99-112]. The X-ray crystal structure of the ternary complex of trypsinogen-[Arg15]PTI with the dipeptide Val-Val has been determined by X-ray data to 2.2-A (0.22-nm) resolution by means of difference Fourier methods and has been crystallographically refined to a final R-value of 0.17. Replacement of the reactive-site Lys15 by an arginine residue is accompanied in the complex by small movements of polar side groups of trypsin and enclosed solvent molecules within the specificity pocket. Only solvent molecule 414 OH which mediates the hydrogen bond interactions between Lys15 NZ and Asp189 carboxylate is expelled, thus allowing the bulkier guanidyl group to approach this carboxylate. The dipeptide Val-Val binds in the pocket accepting the Ile-Val N-terminus in trypsin. The cavity left by the CD-methyl group of Ile16 upon replacement by a valine residue is only partially filled by slight rearrangements of neighbouring peptide side chains. Part of the positive free energy change observed upon replacement of Ile-Val may allow for the maintenance of this cavity.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
16807918 K.Segers, J.Rosing, and G.A.Nicolaes (2006).
Structural models of the snake venom factor V activators from Daboia russelli and Daboia lebetina.
  Proteins, 64, 968-984.
PDB codes: 2fjo 2fjq
15759084 A.Gudmundsdóttir, and H.M.Pálsdóttir (2005).
Atlantic cod trypsins: from basic research to practical applications.
  Mar Biotechnol (NY), 7, 77-88.  
16384030 D.Ming, and M.E.Wall (2005).
Allostery in a coarse-grained model of protein dynamics.
  Phys Rev Lett, 95, 198103.  
15578663 O.Guvench, D.J.Price, and C.L.Brooks (2005).
Receptor rigidity and ligand mobility in trypsin-ligand complexes.
  Proteins, 58, 407-417.  
11439186 A.B.Bicknell, K.Lomthaisong, R.J.Woods, E.G.Hutchinson, H.P.Bennett, R.T.Gladwell, and P.J.Lowry (2001).
Characterization of a serine protease that cleaves pro-gamma-melanotropin at the adrenal to stimulate growth.
  Cell, 105, 903-912.  
11223512 T.Hori, T.Kumasaka, M.Yamamoto, N.Nonaka, N.Tanaka, Y.Hashimoto, U.Ueki, and K.Takio (2001).
Structure of a new 'aspzincin' metalloendopeptidase from Grifola frondosa: implications for the catalytic mechanism and substrate specificity based on several different crystal forms.
  Acta Crystallogr D Biol Crystallogr, 57, 361-368.
PDB codes: 1g12 1ge5 1ge6 1ge7
10716920 G.Barbato, D.O.Cicero, F.Cordier, F.Narjes, B.Gerlach, S.Sambucini, S.Grzesiek, V.G.Matassa, R.De Francesco, and R.Bazzo (2000).
Inhibitor binding induces active site stabilization of the HCV NS3 protein serine protease domain.
  EMBO J, 19, 1195-1206.
PDB code: 1dxw
10944388 V.Z.Pletnev, T.S.Zamolodchikova, W.A.Pangborn, and W.L.Duax (2000).
Crystal structure of bovine duodenase, a serine protease, with dual trypsin and chymotrypsin-like specificities.
  Proteins, 41, 8.
PDB code: 1euf
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.  
  9445056 T.L.McInerney, W.El Ahmar, B.E.Kemp, and P.Poumbourios (1998).
Mutation-directed chemical cross-linking of human immunodeficiency virus type 1 gp41 oligomers.
  J Virol, 72, 1523-1533.  
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
  9188600 J.Xu, E.Mendez, P.R.Caron, C.Lin, M.A.Murcko, M.S.Collett, and C.M.Rice (1997).
Bovine viral diarrhea virus NS3 serine proteinase: polyprotein cleavage sites, cofactor requirements, and molecular model of an enzyme essential for pestivirus replication.
  J Virol, 71, 5312-5322.  
18629959 T.Makriyannis, and Y.D.Clonis (1997).
Design and study of peptide-ligand affinity chromatography adsorbents: Application to the case of trypsin purification from bovine pancreas.
  Biotechnol Bioeng, 53, 49-57.  
  7489704 A.van de Locht, D.Lamba, M.Bauer, R.Huber, T.Friedrich, B.Kröger, W.Höffken, and W.Bode (1995).
Two heads are better than one: crystal structure of the insect derived double domain Kazal inhibitor rhodniin in complex with thrombin.
  EMBO J, 14, 5149-5157.
PDB codes: 1tbq 1tbr
  7795518 J.J.Perona, and C.S.Craik (1995).
Structural basis of substrate specificity in the serine proteases.
  Protein Sci, 4, 337-360.
PDB code: 1amh
7592708 M.S.Dennis, A.Herzka, and R.A.Lazarus (1995).
Potent and selective Kunitz domain inhibitors of plasma kallikrein designed by phage display.
  J Biol Chem, 270, 25411-25417.  
8302861 E.Pizzi, A.Tramontano, L.Tomei, N.La Monica, C.Failla, M.Sardana, T.Wood, and R.De Francesco (1994).
Molecular model of the specificity pocket of the hepatitis C virus protease: implications for substrate recognition.
  Proc Natl Acad Sci U S A, 91, 888-892.  
1541261 W.Bode, and R.Huber (1992).
Natural protein proteinase inhibitors and their interaction with proteinases.
  Eur J Biochem, 204, 433-451.  
2226434 W.Bode, D.Turk, and J.Stürzebecher (1990).
Geometry of binding of the benzamidine- and arginine-based inhibitors N alpha-(2-naphthyl-sulphonyl-glycyl)-DL-p-amidinophenylalanyl-pipe ridine (NAPAP) and (2R,4R)-4-methyl-1-[N alpha-(3-methyl-1,2,3,4-tetrahydro-8- quinolinesulphonyl)-L-arginyl]-2-piperidine carboxylic acid (MQPA) to human alpha-thrombin. X-ray crystallographic determination of the NAPAP-trypsin complex and modeling of NAPAP-thrombin and MQPA-thrombin.
  Eur J Biochem, 193, 175-182.
PDB code: 1ppc
2475133 J.Beckmann, A.Mehlich, W.Schröder, H.R.Wenzel, and H.Tschesche (1989).
Semisynthesis of Arg15, Glu15, Met15, and Nle15-aprotinin involving enzymatic peptide bond resynthesis.
  J Protein Chem, 8, 101-113.  
2715796 M.Tintelnot, and P.Andrews (1989).
Geometries of functional group interactions in enzyme-ligand complexes: guides for receptor modelling.
  J Comput Aided Mol Des, 3, 67-84.  
  2583108 W.Bode, I.Mayr, U.Baumann, R.Huber, S.R.Stone, and J.Hofsteenge (1989).
The refined 1.9 A crystal structure of human alpha-thrombin: interaction with D-Phe-Pro-Arg chloromethylketone and significance of the Tyr-Pro-Pro-Trp insertion segment.
  EMBO J, 8, 3467-3475.
PDB code: 1ppb
3273224 P.Ascenzi, M.Coletta, G.Amiconi, M.Bolognesi, M.Guarneri, and E.Menegatti (1988).
Zymogen activation: effect of peptides sequentially related to the bovine beta-trypsin N-terminus on Kazal inhibitor and benzamidine binding to bovine trypsinogen.
  J Mol Recognit, 1, 130-137.  
3063392 S.R.Sprang, R.J.Fletterick, L.Gráf, W.J.Rutter, and C.S.Craik (1988).
Studies of specificity and catalysis in trypsin by structural analysis of site-directed mutants.
  Crit Rev Biotechnol, 8, 225-236.  
3553217 C.S.Craik, S.Roczniak, S.Sprang, R.Fletterick, and W.Rutter (1987).
Redesigning trypsin via genetic engineering.
  J Cell Biochem, 33, 199-211.  
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.

 

spacer
spacer