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PDBsum entry 1kls

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protein metals links
Transcription PDB id
1kls
Jmol
Contents
Protein chain
30 a.a. *
Metals
_ZN
* Residue conservation analysis
PDB id:
1kls
Name: Transcription
Title: Nmr structure of the zfy-6t[y10l] zinc finger
Structure: Zinc finger y-chromosomal protein. Chain: a. Engineered: yes. Mutation: yes
Source: Synthetic: yes. Other_details: this peptide was synthesized by solid-phase synthesis. The sequence of the peptide is naturally found in homo sapiens (human).
NMR struc: 30 models
Authors: M.J.Lachenmann,J.E.Ladbury,N.B.Phillips,N.Narayana,X.Qian, M.A.Weiss
Key ref:
M.J.Lachenmann et al. (2002). The hidden thermodynamics of a zinc finger. J Mol Biol, 316, 969-989. PubMed id: 11884136 DOI: 10.1006/jmbi.2001.5335
Date:
12-Dec-01     Release date:   13-Mar-02    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P08048  (ZFY_HUMAN) -  Zinc finger Y-chromosomal protein
Seq:
Struc:
 
Seq:
Struc:
801 a.a.
30 a.a.*
Key:    PfamA domain  Secondary structure
* PDB and UniProt seqs differ at 3 residue positions (black crosses)

 

 
DOI no: 10.1006/jmbi.2001.5335 J Mol Biol 316:969-989 (2002)
PubMed id: 11884136  
 
 
The hidden thermodynamics of a zinc finger.
M.J.Lachenmann, J.E.Ladbury, N.B.Phillips, N.Narayana, X.Qian, M.A.Weiss.
 
  ABSTRACT  
 
The Zn finger provides a model for studies of protein structure and stability. Its core contains a conserved phenylalanine residue adjoining three architectural elements: a beta-hairpin, an alpha-helix and a tetrahedral Zn(2+)-binding site. Here, we demonstrate that the consensus Phe is not required for high-affinity Zn(2+) binding but contributes to the specification of a precise DNA-binding surface. Substitution of Phe by leucine in a ZFY peptide permits Zn(2+)-dependent folding. Although a native-like structure is retained, structural fluctuations lead to attenuation of selected nuclear Overhauser enhancements and accelerated amide proton exchange. Surprisingly, wild-type Zn affinity is maintained by entropy-enthalpy compensation (EEC): a hidden entropy penalty (TDeltaDeltaS 7kcal/mol) is balanced by enhanced enthalpy of association (DeltaDeltaH -7kcal/mol) at 25 degrees C. Because the variant is less well ordered than the Phe-anchored domain, the net change in entropy is opposite to the apparent change in configurational entropy. By analogy to the thermodynamics of organometallic complexation, we propose that EEC arises from differences in solvent reorganization. Exclusion of Leu among biological sequences suggests an evolutionary constraint on the dynamics of a Zn finger.
 
  Selected figure(s)  
 
Figure 1.
Figure 1. (a) A ribbon model of the parent Zn finger showing Zn 2+ (blue sphere), ligands (two cysteine and two histidine side-chains; light blue), conserved leucine (L, light blue), and central aromatic side- chain (F10; red and asterisk). The C terminus of the peptide is indi- cated. (b) A CPK model of the parent Zn finger showing the edge of F10 in the potential crevice (dark blue); the remainder of the surface is shown in aquamarine. (c) A rep- resentation of parent (F10) and variant (L10) fingers. The side- chains shown in (a) are shaded. The numbering scheme refers to the synthetic peptide (30 residues 19 ). (d) CD spectra of Zn 2+ - free peptides (F10, continuous line; and L10 dashed line) and Zn 2+ - bound peptides: wild-type (Phe; filled circles) and variant (Leu; open circles). CD spectra were obtained at 25 ° C at a peptide con- centration of 100 mM.
Figure 3.
Figure 3. The 1D 1 H-NMR spec- tra of the (a) parent Zn finger and (b) variant Zn finger at 500 MHz and 25 °C. Asterisks in (b) indicate upfield methyl resonances of L10. The upfield region of the wild-type spectrum is remarkable for the b-methylene protons of K25 (labeled in (a)). Arrow indicates down-field amide resonance of Y7, a characteristic feature of Zn fingers. 17
 
  The above figures are reprinted by permission from Elsevier: J Mol Biol (2002, 316, 969-989) copyright 2002.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
17013819 I.V.Smirnov, and R.H.Shafer (2007).
Electrostatics dominate quadruplex stability.
  Biopolymers, 85, 91.  
16379012 E.Vinolo, H.Sebban, A.Chaffotte, A.Israël, G.Courtois, M.Véron, and F.Agou (2006).
A point mutation in NEMO associated with anhidrotic ectodermal dysplasia with immunodeficiency pathology results in destabilization of the oligomer and reduces lipopolysaccharide- and tumor necrosis factor-mediated NF-kappa B activation.
  J Biol Chem, 281, 6334-6348.  
16382145 W.Zhang, B.Li, R.Singh, U.Narendra, L.Zhu, and M.A.Weiss (2006).
Regulation of sexual dimorphism: mutational and chemogenetic analysis of the doublesex DM domain.
  Mol Cell Biol, 26, 535-547.  
15731390 S.B.Dixit, D.Q.Andrews, and D.L.Beveridge (2005).
Induced fit and the entropy of structural adaptation in the complexation of CAP and lambda-repressor with cognate DNA sequences.
  Biophys J, 88, 3147-3157.  
15608125 S.D.Sharrow, K.A.Edmonds, M.A.Goodman, M.V.Novotny, and M.J.Stone (2005).
Thermodynamic consequences of disrupting a water-mediated hydrogen bond network in a protein:pheromone complex.
  Protein Sci, 14, 249-256.  
15557258 M.J.Lachenmann, J.E.Ladbury, X.Qian, K.Huang, R.Singh, and M.A.Weiss (2004).
Solvation and the hidden thermodynamics of a zinc finger probed by nonstandard repair of a protein crevice.
  Protein Sci, 13, 3115-3126.
PDB code: 1xrz
12493736 E.Merithew, C.Stone, S.Eathiraj, and D.G.Lambright (2003).
Determinants of Rab5 interaction with the N terminus of early endosome antigen 1.
  J Biol Chem, 278, 8494-8500.  
12804117 H.R.Chrisman, and D.J.Tindall (2003).
Identification and characterization of a consensus DNA binding element for the zinc finger transcription factor TIEG/EGRalpha.
  DNA Cell Biol, 22, 187-199.  
14732929 M.J.Cliff, and J.E.Ladbury (2003).
A survey of the year 2002 literature on applications of isothermal titration calorimetry.
  J Mol Recognit, 16, 383-391.  
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.