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PDBsum entry 2fs8
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protein ligands Protein-protein interface(s) links
Hydrolase PDB id
2fs8

 

 

 

 

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Contents
Protein chain
243 a.a. *
Ligands
C3A ×4
Waters ×196
* Residue conservation analysis
PDB id:
2fs8
Name: Hydrolase
Title: Human beta-tryptase ii with inhibitor cra-29382
Structure: Tryptase beta-2. Chain: a, b, c, d. Synonym: tryptase-2, tryptase ii. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: tpsb2, tps2. Expressed in: pichia pastoris. Expression_system_taxid: 4922
Biol. unit: Dimer (from PQS)
Resolution:
2.50Å     R-factor:   0.205     R-free:   0.250
Authors: J.R.Somoza
Key ref:
M.E.McGrath et al. (2006). Structure-guided design of peptide-based tryptase inhibitors. Biochemistry, 45, 5964-5973. PubMed id: 16681368 DOI: 10.1021/bi060173m
Date:
21-Jan-06     Release date:   21-Mar-06    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
P20231  (TRYB2_HUMAN) -  Tryptase beta-2 from Homo sapiens
Seq:
Struc: 		275 a.a.
243 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 4 residue positions (black crosses)

 Enzyme reactions 
   Enzyme class: E.C.3.4.21.59  - tryptase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: Preferential cleavage: Arg-|-, Lys-|-, but with more restricted specificity than trypsin.

 

 
DOI no: 10.1021/bi060173m Biochemistry 45:5964-5973 (2006)
PubMed id: 16681368  
 
 
Structure-guided design of peptide-based tryptase inhibitors.
M.E.McGrath, P.A.Sprengeler, B.Hirschbein, J.R.Somoza, I.Lehoux, J.W.Janc, E.Gjerstad, M.Graupe, A.Estiarte, C.Venkataramani, Y.Liu, R.Yee, J.D.Ho, M.J.Green, C.S.Lee, L.Liu, V.Tai, J.Spencer, D.Sperandio, B.A.Katz.
 
  ABSTRACT  
 
Improved peptide-based inhibitors of human beta tryptase were discovered using information gleaned from tripeptide library screening and structure-guided design methods, including fragment screening. Our efforts sought to improve this class of inhibitors by replacing the traditional Lys or Arg P1 element. The optimized compounds display low nanomolar potency against the mast cell target and several hundred-fold selectivity with respect to serine protease off targets. Thus, replacement of Lys/Arg at P1 in a peptide-like scaffold does not need to be accompanied by a loss in target affinity.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
20167486 M.Berg, P.Van der Veken, J.Joossens, V.Muthusamy, M.Breugelmans, C.X.Moss, J.Rudolf, P.Cos, G.H.Coombs, L.Maes, A.Haemers, J.C.Mottram, and K.Augustyns (2010).
Design and evaluation of Trypanosoma brucei metacaspase inhibitors.
  Bioorg Med Chem Lett, 20, 2001-2006.  
18392772 M.Koprowska-Ratajska, A.Kluczyk, P.Stefanowicz, H.Bartosz-Bechowski, and Z.Szewczuk (2009).
Solid phase synthesis of peptides containing novel amino acids, substituted 3-benzimidazolealanines.
  Amino Acids, 36, 309-315.  
17221202 M.Ueda, T.Kubo, K.Miyatake, and T.Nakamura (2007).
Purification and characterization of fibrinolytic alkaline protease from Fusarium sp. BLB.
  Appl Microbiol Biotechnol, 74, 331-338.  
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.

 

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