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PDBsum entry 1slu

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protein ligands metals Protein-protein interface(s) links
Complex (serine protease/inhibitor) PDB id
1slu
Jmol
Contents
Protein chains
131 a.a. *
216 a.a. *
Ligands
ACT
Metals
_CA
Waters ×137
* Residue conservation analysis
PDB id:
1slu
Name: Complex (serine protease/inhibitor)
Title: Rat anionic n143h, e151h trypsin complexed to a86h ecotin
Structure: Ecotin. Chain: a. Synonym: trypsin inhibitor. Engineered: yes. Mutation: yes. Anionic trypsin. Chain: b. Engineered: yes. Mutation: yes
Source: Escherichia coli. Organism_taxid: 562. Expressed in: escherichia coli. Expression_system_taxid: 562. Rattus norvegicus. Norway rat. Organism_taxid: 10116. Expressed in: saccharomyces cerevisiae. Expression_system_taxid: 4932.
Biol. unit: Tetramer (from PQS)
Resolution:
1.80Å     R-factor:   0.193     R-free:   0.285
Authors: L.S.Brinen,R.J.Fletterick
Key ref:
L.S.Brinen et al. (1996). X-ray structures of a designed binding site in trypsin show metal-dependent geometry. Biochemistry, 35, 5999-6009. PubMed id: 8634241 DOI: 10.1021/bi9530200
Date:
07-Feb-96     Release date:   11-Jul-96    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P23827  (ECOT_ECOLI) -  Ecotin
Seq:
Struc:
162 a.a.
131 a.a.*
Protein chain
Pfam   ArchSchema ?
P00763  (TRY2_RAT) -  Anionic trypsin-2
Seq:
Struc:
246 a.a.
216 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 3 residue positions (black crosses)

 Enzyme reactions 
   Enzyme class: Chain B: 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     cellular_component   5 terms 
  Biological process     digestion   6 terms 
  Biochemical function     catalytic activity     10 terms  

 

 
DOI no: 10.1021/bi9530200 Biochemistry 35:5999-6009 (1996)
PubMed id: 8634241  
 
 
X-ray structures of a designed binding site in trypsin show metal-dependent geometry.
L.S.Brinen, W.S.Willett, C.S.Craik, R.J.Fletterick.
 
  ABSTRACT  
 
The three-dimensional structures of complexes of trypsin N143H, E151H bound to ecotin A86H are determined at 2.0 A resolution via X-ray crystallography in the absence and presence of the transition metals Zn2+, Ni2+, and Cu2+. The binding site for these transition metals was constructed by substitution of key amino acids with histidine at the trypsin-ecotin interface in the S2'/P2' pocket. Three histidine side chains, two on trypsin at positions 143 and 151 and one on ecotin at position 86, anchor the metals and provide extended catalytic recognition for substrates with His in the P2' pocket. Comparisons of the three-dimensional structures show the different geometries that result upon the binding of metal in the engineered tridentate site and suggest a structural basis for the kinetics of the metal-regulated catalysis. Of the three metals, the binding of zinc results in the most favorable binding geometry, not dissimilar to those observed in naturally occurring zinc binding proteins.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
20966251 F.Hu, W.Luo, and M.Hong (2010).
Mechanisms of proton conduction and gating in influenza M2 proton channels from solid-state NMR.
  Science, 330, 505-508.  
20711192 M.Schmidt, B.Raghavan, V.Müller, T.Vogl, G.Fejer, S.Tchaptchet, S.Keck, C.Kalis, P.J.Nielsen, C.Galanos, J.Roth, A.Skerra, S.F.Martin, M.A.Freudenberg, and M.Goebeler (2010).
Crucial role for human Toll-like receptor 4 in the development of contact allergy to nickel.
  Nat Immunol, 11, 814-819.  
12808236 E.Toyota, H.Sekizaki, K.Itoh, and K.Tanizawa (2003).
Synthesis and evaluation of guanidine-containing Schiff base copper(II), zinc(II), and iron(III) chelates as trypsin inhibitors.
  Chem Pharm Bull (Tokyo), 51, 625-629.  
11933060 H.Hegyi, J.Lin, D.Greenbaum, and M.Gerstein (2002).
Structural genomics analysis: characteristics of atypical, common, and horizontally transferred folds.
  Proteins, 47, 126-141.  
11854268 N.S.Quinsey, J.C.Whisstock, B.Le Bonniec, V.Louvain, S.P.Bottomley, and R.N.Pike (2002).
Molecular determinants of the mechanism underlying acceleration of the interaction between antithrombin and factor Xa by heparin pentasaccharide.
  J Biol Chem, 277, 15971-15978.  
11055415 T.Tanaka, Y.Kikuchi, H.Matsuzawa, and T.Ohta (2000).
Application of a metal switch to aqualysin I, a subtilisin-type bacterial serine protease, to the S3 site residues, ser102 and gly131.
  Biosci Biotechnol Biochem, 64, 2008-2011.  
9920869 I.S.Efimova, A.Salminen, P.Pohjanjoki, J.Lapinniemi, N.N.Magretova, B.S.Cooperman, A.Goldman, R.Lahti, and A.A.Baykov (1999).
Directed mutagenesis studies of the metal binding site at the subunit interface of Escherichia coli inorganic pyrophosphatase.
  J Biol Chem, 274, 3294-3299.  
9665160 H.W.Hellinga (1998).
Computational protein engineering.
  Nat Struct Biol, 5, 525-527.  
9667915 J.L.Harris, and C.S.Craik (1998).
Engineering enzyme specificity.
  Curr Opin Chem Biol, 2, 127-132.  
9275172 R.Balakrishnan, N.Ramasubbu, K.I.Varughese, and R.Parthasarathy (1997).
Crystal structures of the copper and nickel complexes of RNase A: metal-induced interprotein interactions and identification of a novel copper binding motif.
  Proc Natl Acad Sci U S A, 94, 9620-9625.
PDB code: 1aqp
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 code is shown on the right.