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PDBsum entry 1trm
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protein ligands metals Protein-protein interface(s) links
Hydrolase (serine proteinase) PDB id
1trm

 

 

 

 

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Contents
Protein chains
223 a.a. *
Ligands
BEN ×2
Metals
_CA ×2
Waters ×230
* Residue conservation analysis
PDB id:
1trm
Name: Hydrolase (serine proteinase)
Title: The three-dimensional structure of asn102 mutant of trypsin. Role of asp102 in serine protease catalysis
Structure: Trypsin. Chain: a, b. Engineered: yes
Source: Rattus rattus. Black rat. Organism_taxid: 10117
Resolution:
2.30Å     R-factor:   0.160    
Authors: S.Sprang,T.Standing,R.J.Fletterick
Key ref: S.Sprang et al. (1987). The three-dimensional structure of Asn102 mutant of trypsin: role of Asp102 in serine protease catalysis. Science, 237, 905-909. PubMed id: 3112942 DOI: 10.1126/science.3112942
Date:
21-Oct-87     Release date:   16-Jul-88    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
P00763  (TRY2_RAT) -  Anionic trypsin-2 from Rattus norvegicus
Seq:
Struc: 		246 a.a.
223 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 1 residue position (black cross)

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

 

 
DOI no: 10.1126/science.3112942 Science 237:905-909 (1987)
PubMed id: 3112942  
 
 
The three-dimensional structure of Asn102 mutant of trypsin: role of Asp102 in serine protease catalysis.
S.Sprang, T.Standing, R.J.Fletterick, R.M.Stroud, J.Finer-Moore, N.H.Xuong, R.Hamlin, W.J.Rutter, C.S.Craik.
 
  ABSTRACT  
 
The structure of the Asn102 mutant of trypsin was determined in order to distinguish whether the reduced activity of the mutant at neutral pH results from an altered active site conformation or from an inability to stabilize a positive charge on the active site histidine. The active site structure of the Asn102 mutant of trypsin is identical to the native enzyme with respect to the specificity pocket, the oxyanion hole, and the orientation of the nucleophilic serine. The observed decrease in rate results from the loss of nucleophilicity of the active site serine. This decreased nucleophilicity may result from stabilization of a His57 tautomer that is unable to accept the serine hydroxyl proton.
 

Literature references that cite this PDB file's key reference

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PDB code: 1y7m
16571831 S.L.Smits, E.J.Snijder, and R.J.de Groot (2006).
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PDB code: 1wqs
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PDB codes: 1ild 1ilz 1im0
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PDB codes: 3tgi 3tgj
10022823 H.Jing, K.J.Macon, D.Moore, L.J.DeLucas, J.E.Volanakis, and S.V.Narayana (1999).
Structural basis of profactor D activation: from a highly flexible zymogen to a novel self-inhibited serine protease, complement factor D.
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PDB code: 1fdp
10089353 K.Sekar, R.Biswas, Y.Li, M.Tsai, and M.Sundaralingam (1999).
Structures of the catalytic site mutants D99A and H48Q and the calcium-loop mutant D49E of phospholipase A2.
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PDB codes: 1kvw 1kvx 1kvy
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Molecular mechanisms for the conversion of zymogens to active proteolytic enzymes.
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9636030 L.W.Schultz, D.J.Quirk, and R.T.Raines (1998).
His...Asp catalytic dyad of ribonuclease A: structure and function of the wild-type, D121N, and D121A enzymes.
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PDB codes: 3rsd 4rsd
9236003 G.H.Krooshof, E.M.Kwant, J.Damborský, J.Koca, and D.B.Janssen (1997).
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8639494 C.C.Huang,, C.A.Lesburg, L.L.Kiefer, C.A.Fierke, and D.W.Christianson (1996).
Reversal of the hydrogen bond to zinc ligand histidine-119 dramatically diminishes catalysis and enhances metal equilibration kinetics in carbonic anhydrase II.
  Biochemistry, 35, 3439-3446.
PDB codes: 1zsa 1zsb 1zsc
8672429 D.Brömme, P.R.Bonneau, E.Purisima, P.Lachance, S.Hajnik, D.Y.Thomas, and A.C.Storer (1996).
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Complement factor D, a novel serine protease.
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8548458 J.J.Tesmer, T.J.Klem, M.L.Deras, V.J.Davisson, and J.L.Smith (1996).
The crystal structure of GMP synthetase reveals a novel catalytic triad and is a structural paradigm for two enzyme families.
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PDB code: 1gpm
8605201 L.Hedstrom, T.Y.Lin, and W.Fast (1996).
Hydrophobic interactions control zymogen activation in the trypsin family of serine proteases.
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8679620 M.Gondry, and F.Lederer (1996).
Functional properties of the histidine-aspartate ion pair of flavocytochrome b2 (L-lactate dehydrogenase): substitution of Asp282 with asparagine.
  Biochemistry, 35, 8587-8594.  
8605210 R.R.Annand, M.Kontoyianni, J.E.Penzotti, T.Dudler, T.P.Lybrand, and M.H.Gelb (1996).
Active site of bee venom phospholipase A2: the role of histidine-34, aspartate-64 and tyrosine-87.
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The picornaviral 3C proteinases: cysteine nucleophiles in serine proteinase folds.
  Protein Sci, 4, 1439-1445.  
  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
7773790 Y.Wei, J.L.Schottel, U.Derewenda, L.Swenson, S.Patkar, and Z.S.Derewenda (1995).
A novel variant of the catalytic triad in the Streptomyces scabies esterase.
  Nat Struct Biol, 2, 218-223.
PDB codes: 1esc 1esd 1ese
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Structure and function of the catalytic site mutant Asp 99 Asn of phospholipase A2: absence of the conserved structural water.
  Protein Sci, 3, 2082-2088.
PDB code: 1ceh
7846025 A.O.Smalås, E.S.Heimstad, A.Hordvik, N.P.Willassen, and R.Male (1994).
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PDB code: 2tbs
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Mutational analysis of the Drosophila snake protease: an essential role for domains within the proenzyme polypeptide chain.
  Genetics, 136, 1355-1365.  
  8156987 M.E.McGrath, T.Erpel, C.Bystroff, and R.J.Fletterick (1994).
Macromolecular chelation as an improved mechanism of protease inhibition: structure of the ecotin-trypsin complex.
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7815089 N.Tomioka, and A.Itai (1994).
GREEN: a program package for docking studies in rational drug design.
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8223632 A.Gudmundsdóttir, E.Gudmundsdóttir, S.Oskarsson, J.B.Bjarnason, A.K.Eakin, and C.S.Craik (1993).
Isolation and characterization of cDNAs from Atlantic cod encoding two different forms of trypsinogen.
  Eur J Biochem, 217, 1091-1097.  
8446599 M.H.Tai, S.S.Chirala, and S.J.Wakil (1993).
Roles of Ser101, Asp236, and His237 in catalysis of thioesterase II and of the C-terminal region of the enzyme in its interaction with fatty acid synthase.
  Proc Natl Acad Sci U S A, 90, 1852-1856.  
8332606 S.Nakagawa, H.A.Yu, M.Karplus, and H.Umeyama (1993).
Active site dynamics of acyl-chymotrypsin.
  Proteins, 16, 172-194.  
  8302216 W.G.Dougherty, and B.L.Semler (1993).
Expression of virus-encoded proteinases: functional and structural similarities with cellular enzymes.
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1310695 D.T.Hung, T.K.Vu, V.I.Wheaton, I.F.Charo, N.A.Nelken, N.Esmon, C.T.Esmon, and S.R.Coughlin (1992).
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2040286 A.J.Horrevoets, H.M.Verheij, and G.H.de Haas (1991).
Inactivation of Escherichia coli outer-membrane phospholipase A by the affinity label hexadecanesulfonyl fluoride. Evidence for an active-site serine.
  Eur J Biochem, 198, 247-253.  
1862088 E.Krejci, N.Duval, A.Chatonnet, P.Vincens, and J.Massoulié (1991).
Cholinesterase-like domains in enzymes and structural proteins: functional and evolutionary relationships and identification of a catalytically essential aspartic acid.
  Proc Natl Acad Sci U S A, 88, 6647-6651.  
1658804 M.A.Lawson, and B.L.Semler (1991).
Poliovirus thiol proteinase 3C can utilize a serine nucleophile within the putative catalytic triad.
  Proc Natl Acad Sci U S A, 88, 9919-9923.  
1896458 M.T.Cederholm, J.A.Stuckey, M.S.Doscher, and L.Lee (1991).
Histidine pKa shifts accompanying the inactivating Asp121----Asn substitution in a semisynthetic bovine pancreatic ribonuclease.
  Proc Natl Acad Sci U S A, 88, 8116-8120.  
1849488 N.Kato, M.Hijikata, M.Nakagawa, Y.Ootsuyama, K.Muraiso, S.Ohkoshi, and K.Shimotohno (1991).
Molecular structure of the Japanese hepatitis C viral genome.
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1881877 T.Earnest, E.Fauman, C.S.Craik, and R.Stroud (1991).
1.59 A structure of trypsin at 120 K: comparison of low temperature and room temperature structures.
  Proteins, 10, 171-187.
PDB code: 1dpo
1814362 W.S.Blair, and B.L.Semler (1991).
Self-cleaving proteases.
  Curr Opin Cell Biol, 3, 1039-1045.  
2199972 B.Katz, and A.A.Kossiakoff (1990).
Crystal structures of subtilisin BPN' variants containing disulfide bonds and cavities: concerted structural rearrangements induced by mutagenesis.
  Proteins, 7, 343-357.  
  2335827 C.S.Hahn, and J.H.Strauss (1990).
Site-directed mutagenesis of the proposed catalytic amino acids of the Sindbis virus capsid protein autoprotease.
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2275978 M.Geller, G.Carlson-Golab, B.Lesyng, S.M.Swanson, and E.F.Meyer (1990).
Dynamic properties of the first enzymatic reaction steps of porcine pancreatic elastase. How rigid is the active site of the native enzyme? Molecular dynamics simulation.
  Biopolymers, 30, 781-796.  
2658216 A.R.Clarke, T.Atkinson, and J.J.Holbrook (1989).
From analysis to synthesis: new ligand binding sites on the lactate dehydrogenase framework. Part I.
  Trends Biochem Sci, 14, 101-105.  
  2667896 C.B.Newgard, P.K.Hwang, and R.J.Fletterick (1989).
The family of glycogen phosphorylases: structure and function.
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2651464 J.R.Vasquez, L.B.Evnin, J.N.Higaki, and C.S.Craik (1989).
An expression system for trypsin.
  J Cell Biochem, 39, 265-276.  
  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.
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3504964 B.Lesyng, and E.F.Meyer (1987).
Energy minimization and molecular dynamics studies of Asn-102 elastase.
  J Comput Aided Mol Des, 1, 211-217.  
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.

 

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