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PDBsum entry 1trn

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Hydrolase (serine proteinase) PDB id
1trn
Jmol
Contents
Protein chain
224 a.a. *
Ligands
ISP ×2
Waters ×301
* Residue conservation analysis
PDB id:
1trn
Name: Hydrolase (serine proteinase)
Title: Crystal structure of human trypsin 1: unexpected phosphorylation of tyrosine 151
Structure: Trypsin. Chain: a, b. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606
Biol. unit: Tetramer (from PQS)
Resolution:
2.20Å     R-factor:   0.177    
Authors: C.Gaboriaud,J.C.Fontecilla-Camps
Key ref:
C.Gaboriaud et al. (1996). Crystal structure of human trypsin 1: unexpected phosphorylation of Tyr151. J Mol Biol, 259, 995. PubMed id: 8683601 DOI: 10.1006/jmbi.1996.0376
Date:
16-Mar-95     Release date:   03-Jun-95    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
P07477  (TRY1_HUMAN) -  Trypsin-1
Seq:
Struc:
247 a.a.
224 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: 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   4 terms 
  Biological process     small molecule metabolic process   8 terms 
  Biochemical function     catalytic activity     6 terms  

 

 
DOI no: 10.1006/jmbi.1996.0376 J Mol Biol 259:995 (1996)
PubMed id: 8683601  
 
 
Crystal structure of human trypsin 1: unexpected phosphorylation of Tyr151.
C.Gaboriaud, L.Serre, O.Guy-Crotte, E.Forest, J.C.Fontecilla-Camps.
 
  ABSTRACT  
 
The X-ray structure of human trypsin 1 has been determined in the presence of diisopropyl-phosphofluoridate by the molecular replacement method and refined at a resolution of 2.2 A to an R-factor of 18%. Crystals belong to the space group P4, with two independent molecules in the asymmetric unit packing as crystallographic tetramers. This study was performed in order to seek possible structural peculiarities of human trypsin 1, suggested by some striking differences in its biochemical behavior as compared to other trypsins of mammalian species. Its fold is, in fact, very similar to those of the bovine, rat and porcine trypsins, with root-mean-square differences in the 0.4 to 0.6 A range for all 223 C alpha positions. The most unexpected feature of the human trypsin 1 structure is in the phosphorylated state of tyrosine residue 151 in the present X-ray study. This feature was confirmed by mass spectrometry on the same inhibited sample and also on the native enzyme. This phosphorylation strengthens the outstanding clustering of highly negative or highly positive electrostatic surface potentials. The peculiar inhibitory behaviour of pancreatic secretory trypsin inhibitors of the Kazal type on this enzyme is discussed as a possible consequence of these properties. A charged surface loop has also been interpreted as an epitope site recognised by a monoclonal antibody specific to human trypsin 1.
 
  Selected figure(s)  
 
Figure 6.
Figure 6. Stereo view of the (2Fo - Fc) electron density map around the active site superposed on the refined model containing the serine-bound diisopropyl phosphate. The electron density map was contoured at the 1s level. Hydrogen bonds are drawn with broken lines.
Figure 7.
Figure 7. Stereo view of the (2Fo - Fc) electron density map around the phosphotyrosine residue 151, superposed on the refined model. The electron density map was contoured at the 1s level. All residues within 5 Å of the Tyr151 hydroxyl group are displayed.
 
  The above figures are reprinted by permission from Elsevier: J Mol Biol (1996, 259, 995-0) copyright 1996.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21543845 A.Sukhwal, M.Bhattacharyya, and S.Vishveshwara (2011).
Network approach for capturing ligand-induced subtle global changes in protein structures.
  Acta Crystallogr D Biol Crystallogr, 67, 429-439.  
21323990 D.N.Reddy, and S.S.Prasad (2011).
Genetic basis of chronic pancreatitis in Asia Pacific region.
  J Gastroenterol Hepatol, 26, 2-5.  
20163205 O.Itkonen (2010).
Human trypsinogens in the pancreas and in cancer.
  Scand J Clin Lab Invest, 70, 136-143.  
19453252 J.M.Chen, and C.Férec (2009).
Chronic pancreatitis: genetics and pathogenesis.
  Annu Rev Genomics Hum Genet, 10, 63-87.  
19140225 S.Mahurkar, D.N.Reddy, G.V.Rao, and G.R.Chandak (2009).
Genetic mechanisms underlying the pathogenesis of tropical calcific pancreatitis.
  World J Gastroenterol, 15, 264-269.  
18986305 Z.Rónai, H.Witt, O.Rickards, G.Destro-Bisol, A.R.Bradbury, and M.Sahin-Tóth (2009).
A common African polymorphism abolishes tyrosine sulfation of human anionic trypsinogen (PRSS2).
  Biochem J, 418, 155-161.  
18077447 M.A.Salameh, A.S.Soares, A.Hockla, and E.S.Radisky (2008).
Structural basis for accelerated cleavage of bovine pancreatic trypsin inhibitor (BPTI) by human mesotrypsin.
  J Biol Chem, 283, 4115-4123.
PDB codes: 2r9p 2ra3
17204147 J.Rosendahl, H.Bödeker, J.Mössner, and N.Teich (2007).
Hereditary chronic pancreatitis.
  Orphanet J Rare Dis, 2, 1.  
17592142 R.Szmola, and M.Sahin-Tóth (2007).
Chymotrypsin C (caldecrin) promotes degradation of human cationic trypsin: identity with Rinderknecht's enzyme Y.
  Proc Natl Acad Sci U S A, 104, 11227-11232.  
17075961 A.Borthakur, E.Mellon, S.Niyogi, W.Witschey, J.B.Kneeland, and R.Reddy (2006).
Sodium and T1rho MRI for molecular and diagnostic imaging of articular cartilage.
  NMR Biomed, 19, 781-821.  
16759229 E.Szepessy, and M.Sahin-Tóth (2006).
Human mesotrypsin exhibits restricted S1' subsite specificity with a strong preference for small polar side chains.
  FEBS J, 273, 2942-2954.  
16699518 H.Witt, M.Sahin-Tóth, O.Landt, J.M.Chen, T.Kähne, J.P.Drenth, Z.Kukor, E.Szepessy, W.Halangk, S.Dahm, K.Rohde, H.U.Schulz, C.Le Maréchal, N.Akar, R.W.Ammann, K.Truninger, M.Bargetzi, E.Bhatia, C.Castellani, G.M.Cavestro, M.Cerny, G.Destro-Bisol, G.Spedini, H.Eiberg, J.B.Jansen, M.Koudova, E.Rausova, M.Macek, N.Malats, F.X.Real, H.J.Menzel, P.Moral, R.Galavotti, P.F.Pignatti, O.Rickards, J.Spicak, N.O.Zarnescu, W.Böck, T.M.Gress, H.Friess, J.Ockenga, H.Schmidt, R.Pfützer, M.Löhr, P.Simon, F.U.Weiss, M.M.Lerch, N.Teich, V.Keim, T.Berg, B.Wiedenmann, W.Luck, D.A.Groneberg, M.Becker, T.Keil, A.Kage, J.Bernardova, M.Braun, C.Güldner, J.Halangk, J.Rosendahl, U.Witt, M.Treiber, R.Nickel, and C.Férec (2006).
A degradation-sensitive anionic trypsinogen (PRSS2) variant protects against chronic pancreatitis.
  Nat Genet, 38, 668-673.  
17087724 M.Sahin-Tóth, Z.Kukor, and Z.Nemoda (2006).
Human cationic trypsinogen is sulfated on Tyr154.
  FEBS J, 273, 5044-5050.  
16632094 M.Sahin-Tóth (2006).
Biochemical models of hereditary pancreatitis.
  Endocrinol Metab Clin North Am, 35, 303.  
16791840 N.Teich, J.Rosendahl, M.Tóth, J.Mössner, and M.Sahin-Tóth (2006).
Mutations of human cationic trypsinogen (PRSS1) and chronic pancreatitis.
  Hum Mutat, 27, 721-730.  
15970597 Z.Nemoda, and M.Sahin-Tóth (2005).
The tetra-aspartate motif in the activation peptide of human cationic trypsinogen is essential for autoactivation control but not for enteropeptidase recognition.
  J Biol Chem, 280, 29645-29652.  
11910039 A.Kahyaoglu, and F.Jordan (2002).
Direct proton magnetic resonance determination of the pKa of the active center histidine in thiolsubtilisin.
  Protein Sci, 11, 965-973.  
12573113 C.Acosta Bas, I.B.Baluja Conde, A.I.Brito Moreno, M.R.Rodríguez López, A.Melchor, L.Hernández, A.Frómeta, M.E.Selles, and L.Martínez (2002).
Monoclonal antibody against human trypsin: production, characterization, and use for diagnosis.
  Hybrid Hybridomics, 21, 487-490.  
12193285 C.Acosta Bas, I.B.Baluja Conde, A.I.Brito Moreno, M.R.Rodriguez Lopez, A.Melchor, L.Hernandez, and A.Frómeta (2002).
Specific monoclonal antibody against human trypsin.
  Hybrid Hybridomics, 21, 307-310.  
11840029 H.Witt, and M.Becker (2002).
Genetics of chronic pancreatitis.
  J Pediatr Gastroenterol Nutr, 34, 125-136.  
11719509 P.Simon, F.U.Weiss, M.Sahin-Toth, M.Parry, O.Nayler, B.Lenfers, J.Schnekenburger, J.Mayerle, W.Domschke, and M.M.Lerch (2002).
Hereditary pancreatitis caused by a novel PRSS1 mutation (Arg-122 --> Cys) that alters autoactivation and autodegradation of cationic trypsinogen.
  J Biol Chem, 277, 5404-5410.  
11788986 T.Rabilloud (2002).
Two-dimensional gel electrophoresis in proteomics: old, old fashioned, but it still climbs up the mountains.
  Proteomics, 2, 3.  
11748242 Z.Kukor, M.Tóth, G.Pál, and M.Sahin-Tóth (2002).
Human cationic trypsinogen. Arg(117) is the reactive site of an inhibitory surface loop that controls spontaneous zymogen activation.
  J Biol Chem, 277, 6111-6117.  
10672012 H.K.Leiros, N.P.Willassen, and A.O.Smalås (2000).
Structural comparison of psychrophilic and mesophilic trypsins. Elucidating the molecular basis of cold-adaptation.
  Eur J Biochem, 267, 1039-1049.  
10707029 J.D.Szustakowski, and Z.Weng (2000).
Protein structure alignment using a genetic algorithm.
  Proteins, 38, 428-440.  
  10446089 D.C.Whitcomb (1999).
Hereditary pancreatitis: new insights into acute and chronic pancreatitis.
  Gut, 45, 317-322.  
9707558 K.P.Hopfner, E.Kopetzki, G.B.Kresse, W.Bode, R.Huber, and R.A.Engh (1998).
New enzyme lineages by subdomain shuffling.
  Proc Natl Acad Sci U S A, 95, 9813-9818.
PDB code: 1fxy
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.