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PDBsum entry 1bty
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Hydrolase PDB id
1bty

 

 

 

 

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Contents
Protein chain
223 a.a. *
Ligands
BEN
Metals
_CA
Waters ×657
* Residue conservation analysis
PDB id:
1bty
Name: Hydrolase
Title: Crystal structure of beta-trypsin in complex with benzamidine
Structure: Beta-trypsin. Chain: a. Ec: 3.4.21.4
Source: Bos taurus. Bovine
Resolution:
1.50Å     R-factor:   0.161    
Authors: R.M.Stroud,B.A.Katz,J.Finer-Moore
Key ref:
B.A.Katz et al. (1995). Episelection: novel Ki approximately nanomolar inhibitors of serine proteases selected by binding or chemistry on an enzyme surface. Biochemistry, 34, 8264-8280. PubMed id: 7599119 DOI: 10.1021/bi00026a008
Date:
17-May-95     Release date:   15-Oct-95    
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.
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.

 

 
DOI no: 10.1021/bi00026a008 Biochemistry 34:8264-8280 (1995)
PubMed id: 7599119  
 
 
Episelection: novel Ki approximately nanomolar inhibitors of serine proteases selected by binding or chemistry on an enzyme surface.
B.A.Katz, J.Finer-Moore, R.Mortezaei, D.H.Rich, R.M.Stroud.
 
  ABSTRACT  
 
A novel class of mechanism-based inhibitors of the serine proteases is developed using epitaxial selection. Tripeptide boronates esterified by an alcohol or alcohols at the boron retain the tight binding to trypsin-like enzymes associated with transition-state analogs and incorporate additional groups that can be utilized for selectivity between proteases. Formed by reaction of a series of alcohols with the inhibitor boronate oxygen(s), the most structurally compatible alcohol-derivatized inhibitors are either selected by binding to the enzyme (epitaxial selection) or assembled by epitaxial reaction on the enzyme surface. Mass spectrometry of the derivatized boronates and X-ray crystallography of the complexes identify the chemical structures and the three-dimensional interactions of inhibitors generated. This scheme also engineers novel, potent (Ki approximately 7 nM), and more specific inhibitors of individual serine proteases, by derivitizations of compounds obtained by epitaxial selection.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
20535822 A.Sircar, S.Chaudhury, K.P.Kilambi, M.Berrondo, and J.J.Gray (2010).
A generalized approach to sampling backbone conformations with RosettaDock for CAPRI rounds 13-19.
  Proteins, 78, 3115-3123.  
21152290 I.H.Moal, and P.A.Bates (2010).
SwarmDock and the Use of Normal Modes in Protein-Protein Docking.
  Int J Mol Sci, 11, 3623-3648.  
20136072 J.W.Ponder, C.Wu, P.Ren, V.S.Pande, J.D.Chodera, M.J.Schnieders, I.Haque, D.L.Mobley, D.S.Lambrecht, R.A.DiStasio, M.Head-Gordon, G.N.Clark, M.E.Johnson, and T.Head-Gordon (2010).
Current status of the AMOEBA polarizable force field.
  J Phys Chem B, 114, 2549-2564.  
20607697 M.Eisenstein, A.Ben-Shimon, Z.Frankenstein, and N.Kowalsman (2010).
CAPRI targets T29-T42: proving ground for new docking procedures.
  Proteins, 78, 3174-3181.  
20597089 S.J.Fleishman, J.E.Corn, E.M.Strauch, T.A.Whitehead, I.Andre, J.Thompson, J.J.Havranek, R.Das, P.Bradley, and D.Baker (2010).
Rosetta in CAPRI rounds 13-19.
  Proteins, 78, 3212-3218.  
20718048 S.J.de Vries, A.S.Melquiond, P.L.Kastritis, E.Karaca, A.Bordogna, M.van Dijk, J.P.Rodrigues, and A.M.Bonvin (2010).
Strengths and weaknesses of data-driven docking in critical assessment of prediction of interactions.
  Proteins, 78, 3242-3249.  
20635420 S.Y.Huang, and X.Zou (2010).
MDockPP: A hierarchical approach for protein-protein docking and its application to CAPRI rounds 15-19.
  Proteins, 78, 3096-3103.  
19399779 D.Jiao, J.Zhang, R.E.Duke, G.Li, M.J.Schnieders, and P.Ren (2009).
Trypsin-ligand binding free energies from explicit and implicit solvent simulations with polarizable potential.
  J Comput Chem, 30, 1701-1711.  
19549826 E.Zakharova, M.P.Horvath, and D.P.Goldenberg (2009).
Structure of a serine protease poised to resynthesize a peptide bond.
  Proc Natl Acad Sci U S A, 106, 11034-11039.
PDB codes: 3fp6 3fp7 3fp8
19965178 Y.Shi, D.Jiao, M.J.Schnieders, and P.Ren (2009).
Trypsin-ligand binding free energy calculation with AMOEBA.
  Conf Proc IEEE Eng Med Biol Soc, 1, 2328-2331.  
17469803 A.Moulin, J.H.Bell, R.F.Pratt, and D.Ringe (2007).
Inhibition of chymotrypsin by a complex of ortho-vanadate and benzohydroxamic acid: structure of the inert complex and its mechanistic interpretation.
  Biochemistry, 46, 5982-5990.
PDB code: 2p8o
16586522 B.de Bruin, P.Hauwert, and J.N.Reek (2006).
Dynamic combinatorial chemistry: the unexpected choice of receptors by guest molecules.
  Angew Chem Int Ed Engl, 45, 2660-2663.  
16902927 H.Nakamura, H.Kuroda, H.Saito, R.Suzuki, T.Yamori, K.Maruyama, and T.Haga (2006).
Synthesis and biological evaluation of boronic acid containing cis-stilbenes as apoptotic tubulin polymerization inhibitors.
  ChemMedChem, 1, 729-740.  
16100736 I.Saur, R.Scopelliti, and K.Severin (2006).
Utilization of self-sorting processes to generate dynamic combinatorial libraries with new network topologies.
  Chemistry, 12, 1058-1066.  
15614799 C.F.Karney, J.E.Ferrara, and S.Brunner (2005).
Method for computing protein binding affinity.
  J Comput Chem, 26, 243-251.  
15185372 T.Asano, H.Nakamura, Y.Uehara, and Y.Yamamoto (2004).
Design, synthesis, and biological evaluation of aminoboronic acids as growth-factor receptor inhibitors of EGFR and VEGFR-1 tyrosine kinases.
  Chembiochem, 5, 483-490.  
12720316 K.N.Rankin, T.Sulea, and E.O.Purisima (2003).
On the transferability of hydration-parametrized continuum electrostatics models to solvated binding calculations.
  J Comput Chem, 24, 954-962.  
12719221 T.Sulea, and E.O.Purisima (2003).
Profiling charge complementarity and selectivity for binding at the protein surface.
  Biophys J, 84, 2883-2896.  
12119606 O.Ramström, and J.M.Lehn (2002).
Drug discovery by dynamic combinatorial libraries.
  Nat Rev Drug Discov, 1, 26-36.  
12116383 S.M.Schwarzl, T.B.Tschopp, J.C.Smith, and S.Fischer (2002).
Can the calculation of ligand binding free energies be improved with continuum solvent electrostatics and an ideal-gas entropy correction?
  J Comput Chem, 23, 1143-1149.  
11353508 R.Nguyen, and I.Huc (2001).
Using an Enzyme's Active Site To Template Inhibitors This work was supported by the Centre National de la Recherche Scientifique and by the Ecole Polytechnique (predoctoral fellowship to R.N.). We thank Prof. Jean-Marie Lehn for stimulating discussions.
  Angew Chem Int Ed Engl, 40, 1774-1776.  
11828475 T.Bunyapaiboonsri, O.Ramström, S.Lohmann, J.M.Lehn, L.Peng, and M.Goeldner (2001).
Dynamic deconvolution of a pre-equilibrated dynamic combinatorial library of acetylcholinesterase inhibitors.
  Chembiochem, 2, 438-444.  
11026541 A.von Matt, C.Ehrhardt, P.Burkhard, R.Metternich, M.Walkinshaw, and C.Tapparelli (2000).
Selective boron-containing thrombin inhibitors--X-ray analysis reveals surprising binding mode.
  Bioorg Med Chem, 8, 2291-2303.  
10652457 I.Karan, and B.L.Miller (2000).
Dynamic diversity in drug discovery: Putting small-molecule evolution to work.
  Drug Discov Today, 5, 67-75.  
  9568894 B.A.Katz, B.Liu, M.Barnes, and E.B.Springman (1998).
Crystal structure of recombinant human tissue kallikrein at 2.0 A resolution.
  Protein Sci, 7, 875-885.  
9772168 E.Skordalakes, S.Elgendy, C.A.Goodwin, D.Green, M.F.Scully, V.V.Kakkar, J.M.Freyssinet, G.Dodson, and J.J.Deadman (1998).
Bifunctional peptide boronate inhibitors of thrombin: crystallographic analysis of inhibition enhanced by linkage to an exosite 1 binding peptide.
  Biochemistry, 37, 14420-14427.
PDB codes: 1a3b 1a3e
9836602 S.R.Presnell, G.S.Patil, C.Mura, K.M.Jude, J.M.Conley, J.A.Bertrand, C.M.Kam, J.C.Powers, and L.D.Williams (1998).
Oxyanion-mediated inhibition of serine proteases.
  Biochemistry, 37, 17068-17081.
PDB codes: 1bju 1bjv
9341205 S.L.Lee, R.S.Alexander, A.Smallwood, R.Trievel, L.Mersinger, P.C.Weber, and C.Kettner (1997).
New inhibitors of thrombin and other trypsin-like proteases: hydrogen bonding of an aromatic cyano group with a backbone amide of the P1 binding site replaces binding of a basic side chain.
  Biochemistry, 36, 13180-13186.
PDB code: 1auj
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.

 

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