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PDBsum entry 2kfb
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Structural protein PDB id
2kfb

 

 

 

 

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Contents
Protein chain
174 a.a. *
* Residue conservation analysis
PDB id:
2kfb
Name: Structural protein
Title: The structure of the cataract causing p23t mutant of human gamma-d crystallin
Structure: Gamma-crystallin d. Chain: a. Synonym: gamma-d-crystallin, gamma-crystallin 4. Engineered: yes. Mutation: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: crygd, cryg4. Expressed in: escherichia coli. Expression_system_taxid: 562. Expression_system_variant: (de3). Other_details: rosetta 2
NMR struc: 20 models
Authors: J.Jung,I.L.Byeon,Y.Wang,J.King,A.M.Gronenborn
Key ref: J.Jung et al. (2009). The structure of the cataract-causing P23T mutant of human gammaD-crystallin exhibits distinctive local conformational and dynamic changes. Biochemistry, 48, 2597-2609. PubMed id: 19216553
Date:
12-Feb-09     Release date:   28-Jul-09    
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 Headers
 References

Protein chain
Pfam   ArchSchema ?
P07320  (CRGD_HUMAN) -  Gamma-crystallin D from Homo sapiens
Seq:
Struc: 		174 a.a.
174 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.?
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]

 

 
Biochemistry 48:2597-2609 (2009)
PubMed id: 19216553  
 
 
The structure of the cataract-causing P23T mutant of human gammaD-crystallin exhibits distinctive local conformational and dynamic changes.
J.Jung, I.J.Byeon, Y.Wang, J.King, A.M.Gronenborn.
 
  ABSTRACT  
 
Crystallins are major proteins of the eye lens and essential for lens transparency. Mutations and aging of crystallins cause cataracts, the predominant cause of blindness in the world. In human gammaD-crystallin, the P23T mutant is associated with congenital cataracts. Until now, no atomic structural information has been available for this variant. Biophysical analyses of this mutant protein have revealed dramatically reduced solubility compared to that of the wild-type protein due to self-association into higher-molecular weight clusters and aggregates that retain a nativelike conformation within the monomers [Pande, A., et al. (2005) Biochemistry 44, 2491-2500]. To elucidate the structure and local conformation around the mutation site, we have determined the solution structure and characterized the protein's dynamic behavior by NMR. Although the global structure is very similar to the X-ray structure of wild-type gammaD-crystallin, pivotal local conformational and dynamic differences are caused by the threonine substitution. In particular, in the P23T mutant, the imidazole ring of His22 switches from the predominant Nepsilon2 tautomer in the wild-type protein to the Ndelta1 tautomer, and an altered motional behavior of the associated region in the protein is observed. The data support structural changes that may initiate aggregation or polymerization by the mutant protein.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
  21465555 M.Sikora, and M.Cieplak (2011).
Mechanical stability of multidomain proteins and novel mechanical clamps.
  Proteins, 79, 1786-1799.  
20382156 S.Lee, B.Mahler, J.Toward, B.Jones, K.Wyatt, L.Dong, G.Wistow, and Z.Wu (2010).
A single destabilizing mutation (F9S) promotes concerted unfolding of an entire globular domain in gammaS-crystallin.
  J Mol Biol, 399, 320-330.  
  21197114 V.P.Vendra, and D.Balasubramanian (2010).
Structural and aggregation behavior of the human γD-crystallin mutant E107A, associated with congenital nuclear cataract.
  Mol Vis, 16, 2822-2828.  
20111584 X.Liu, and Y.P.Zhao (2010).
Switch region for pathogenic structural change in conformational disease and its prediction.
  PLoS One, 5, e8441.  
20639533 Y.M.Kim, and B.S.Choi (2010).
Structure and function of the regulatory HRDC domain from human Bloom syndrome protein.
  Nucleic Acids Res, 38, 7764-7777.
PDB code: 2kv2
20616077 Y.Wang, A.Lomakin, J.J.McManus, O.Ogun, and G.B.Benedek (2010).
Phase behavior of mixtures of human lens proteins Gamma D and Beta B1.
  Proc Natl Acad Sci U S A, 107, 13282-13287.  
19722627 J.Wang, X.Zuo, P.Yu, I.J.Byeon, J.Jung, X.Wang, M.Dyba, S.Seifert, C.D.Schwieters, J.Qin, A.M.Gronenborn, and Y.X.Wang (2009).
Determination of multicomponent protein structures in solution using global orientation and shape restraints.
  J Am Chem Soc, 131, 10507-10515.
PDB codes: 2klj 2klk 2klm
19758984 K.L.Moreau, and J.King (2009).
Hydrophobic core mutations associated with cataract development in mice destabilize human gammaD-crystallin.
  J Biol Chem, 284, 33285-33295.  
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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