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PDBsum entry 1lsn

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Hydrolase(o-glycosyl) PDB id
1lsn
Jmol
Contents
Protein chain
129 a.a. *
Waters ×177
* Residue conservation analysis
PDB id:
1lsn
Name: Hydrolase(o-glycosyl)
Title: Thermal stability determinants of chicken egg-white lysozyme core mutants: hydrophobicity, packing volume and conserved buried water molecules
Structure: Hen egg white lysozyme. Chain: a. Engineered: yes
Source: Gallus gallus. Chicken. Organism_taxid: 9031. Organ: egg
Resolution:
1.90Å     R-factor:   0.150    
Authors: D.R.Holland,P.Shih
Key ref:
P.Shih et al. (1995). Thermal stability determinants of chicken egg-white lysozyme core mutants: hydrophobicity, packing volume, and conserved buried water molecules. Protein Sci, 4, 2050-2062. PubMed id: 8535241 DOI: 10.1002/pro.5560041010
Date:
13-Sep-94     Release date:   30-Nov-94    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P00698  (LYSC_CHICK) -  Lysozyme C
Seq:
Struc:
147 a.a.
129 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 2 residue positions (black crosses)

 Enzyme reactions 
   Enzyme class: E.C.3.2.1.17  - Lysozyme.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: Hydrolysis of the 1,4-beta-linkages between N-acetyl-D-glucosamine and N-acetylmuramic acid in peptidoglycan heteropolymers of the prokaryotes cell walls.
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     extracellular region   2 terms 
  Biological process     metabolic process   4 terms 
  Biochemical function     catalytic activity     6 terms  

 

 
DOI no: 10.1002/pro.5560041010 Protein Sci 4:2050-2062 (1995)
PubMed id: 8535241  
 
 
Thermal stability determinants of chicken egg-white lysozyme core mutants: hydrophobicity, packing volume, and conserved buried water molecules.
P.Shih, D.R.Holland, J.F.Kirsch.
 
  ABSTRACT  
 
A series of 24 mutants was made in the buried core of chicken lysozyme at positions 40, 55, and 91. The midpoint temperature of thermal denaturation transition (Tm) values of these core constructs range from 60.9 to 77.3 degrees C, extending an earlier, more limited investigation on thermostability. The Tm values of variants containing conservative replacements for the wild type (WT) (Thr 40-Ile 55-Ser 91) triplet are linearly correlated with hydrophobicity (r = 0.81) and, to a lesser degree, with combined side-chain volume (r = 0.75). The X-ray structures of the S91A (1.9 A) and I55L/S91T/D101S (1.7 A) mutants are presented. The former amino acid change is found in duck and mammalian lysozymes, and the latter contains the most thermostable core triplet. A network of four conserved, buried water molecules is associated with the core. It is postulated that these water molecules significantly influence the mutational tolerance at the individual triplet positions. The pH dependence of Tm for the S91D mutant was compared with that of WT enzyme. The pKa of S91D is 1.2 units higher in the native than in the denatured state, corresponding to delta delta G298 = 1.7 kcal/mol. This is a low value for charge burial and likely reflects the moderating influence of the buried water molecules or a conformational change. Thermal and chemical denaturation and far UV CD spectroscopy were used to characterize the in vitro properties of I55T. This variant, which buries a hydroxyl group, has similar properties to those of the human amyloidogenic variant I56T.
 
  Selected figure(s)  
 
Figure 1.
Fig. 1. Ribbondrawingshowingthelocations of coreresidues 40, 55, and 91 andtheactivesiteaminoacids 35, 52, nd 101 incickenegg whitelysozyme.Thesidechains f thecoreresiduesand Asp 101 are shownasball-and-stickmodelswithcarbonatomsasgrayandhetero- atomsas blackballs.Thisfigurewasmadewiththe MOLSCRIPT pro- gram(Krulis, 1991).
Figure 4.
Fig. 4. ore region structures compar- ing the packing interactions f (A) TIT and (B) TLT/DlOlS. (The Dl01 locus is outside f the core region.) Dot spheresrepresentingthe vanderWaas surface of Thr 40-Cy2, Ile 88-Cy2, Leu 56-C62,Thr 91-Cy2, andside-chain atom of55 (Ile in A and Leu in ) are shown.Th TIT structur is from Wil sonet al. 1992), andthe TLTIDIOIS structure as determined in this study. PDB codes are IHEM and ILSM, respectively.
 
  The above figures are reprinted from an Open Access publication published by the Protein Society: Protein Sci (1995, 4, 2050-2062) copyright 1995.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
19308329 P.M.Mohan, S.Chakraborty, and R.V.Hosur (2009).
NMR investigations on residue level unfolding thermodynamics in DLC8 dimer by temperature dependent native state hydrogen exchange.
  J Biomol NMR, 44, 1.  
17068801 V.Parthiban, M.M.Gromiha, C.Hoppe, and D.Schomburg (2007).
Structural analysis and prediction of protein mutant stability using distance and torsion potentials: role of secondary structure and solvent accessibility.
  Proteins, 66, 41-52.  
16155198 C.Hoppe, and D.Schomburg (2005).
Prediction of protein thermostability with a direction- and distance-dependent knowledge-based potential.
  Protein Sci, 14, 2682-2692.  
16251276 K.Bajaj, P.Chakrabarti, and R.Varadarajan (2005).
Mutagenesis-based definitions and probes of residue burial in proteins.
  Proc Natl Acad Sci U S A, 102, 16221-16226.  
11354000 M.Joniau, P.Haezebrouck, K.Noyelle, and H.Van Dael (2001).
Structural basis for the appearance of a molten globule state in chimeric molecules derived from lysozyme and alpha-lactalbumin.
  Proteins, 44, 1.  
10813830 A.Rajpal, and J.F.Kirsch (2000).
Role of the minor energetic determinants of chicken egg white lysozyme (HEWL) to the stability of the HEWL.antibody scFv-10 complex.
  Proteins, 40, 49-57.  
10944394 B.Gilquin, C.Guilbert, and D.Perahia (2000).
Unfolding of hen egg lysozyme by molecular dynamics simulations at 300K: insight into the role of the interdomain interface.
  Proteins, 41, 58-74.  
10969021 J.J.Dwyer, A.G.Gittis, D.A.Karp, E.E.Lattman, D.S.Spencer, W.E.Stites, and B.García-Moreno E (2000).
High apparent dielectric constants in the interior of a protein reflect water penetration.
  Biophys J, 79, 1610-1620.  
  10210181 S.K.Kulkarni, A.E.Ashcroft, M.Carey, D.Masselos, C.V.Robinson, and S.E.Radford (1999).
A near-native state on the slow refolding pathway of hen lysozyme.
  Protein Sci, 8, 35-44.  
  9827999 C.P.van Mierlo, W.M.van Dongen, F.Vergeldt, W.J.van Berkel, and E.Steensma (1998).
The equilibrium unfolding of Azotobacter vinelandii apoflavodoxin II occurs via a relatively stable folding intermediate.
  Protein Sci, 7, 2331-2344.  
9265720 B.Lee, and G.Vasmatzis (1997).
Stabilization of protein structures.
  Curr Opin Biotechnol, 8, 423-428.  
9145111 G.Otting, E.Liepinsh, B.Halle, and U.Frey (1997).
NMR identification of hydrophobic cavities with low water occupancies in protein structures using small gas molecules.
  Nat Struct Biol, 4, 396-404.  
  8535242 P.Shih, and J.F.Kirsch (1995).
Design and structural analysis of an engineered thermostable chicken lysozyme.
  Protein Sci, 4, 2063-2072.  
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.