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PDBsum entry 4amh
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Structural protein
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PDB id
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4amh
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PDB id:
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| Name: |
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Structural protein
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Title:
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Influence of circular permutation on the folding pathway of a pdz domain
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Structure:
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Disks large homolog 1. Chain: a, b. Fragment: pdz2 domain. Synonym: synapse-associated protein 97, sap-97, sap97, hdlg. Engineered: yes. Mutation: yes
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Source:
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Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 469008. Expression_system_variant: plyss.
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Resolution:
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2.30Å
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R-factor:
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0.222
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R-free:
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0.268
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Authors:
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G.Hultqvist,A.S.Punekar,C.N.Chi,M.Selmer,S.Gianni,P.Jemth
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Key ref:
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G.Hultqvist
et al.
(2012).
Tolerance of protein folding to a circular permutation in a PDZ domain.
Plos One,
7,
e50055.
PubMed id:
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Date:
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10-Mar-12
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Release date:
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05-Dec-12
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PROCHECK
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Headers
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References
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Q12959
(DLG1_HUMAN) -
Disks large homolog 1 from Homo sapiens
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Seq:
Struc:
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904 a.a.
94 a.a.*
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Key: |
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PfamA domain |
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Secondary structure |
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CATH domain |
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*
PDB and UniProt seqs differ
at 16 residue positions (black
crosses)
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Plos One
7:e50055
(2012)
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PubMed id:
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Tolerance of protein folding to a circular permutation in a PDZ domain.
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G.Hultqvist,
A.S.Punekar,
A.Morrone,
C.N.Chi,
A.Engström,
M.Selmer,
S.Gianni,
P.Jemth.
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ABSTRACT
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Circular permutation is a common molecular mechanism for evolution of proteins.
However, such re-arrangement of secondary structure connectivity may interfere
with the folding mechanism causing accumulation of folding intermediates, which
in turn can lead to misfolding. We solved the crystal structure and investigated
the folding pathway of a circularly permuted variant of a PDZ domain, SAP97
PDZ2. Our data illustrate how well circular permutation may work as a mechanism
for molecular evolution. The circular permutant retains the overall structure
and function of the native protein domain. Further, unlike most examples in the
literature, this circular permutant displays a folding mechanism that is
virtually identical to that of the wild type. This observation contrasts with
previous data on the circularly permuted PDZ2 domain from PTP-BL, for which the
folding pathway was remarkably affected by the same mutation in sequence
connectivity. The different effects of this circular permutation in two
homologous proteins show the strong influence of sequence as compared to
topology. Circular permutation, when peripheral to the major folding nucleus,
may have little effect on folding pathways and could explain why, despite the
dramatic change in primary structure, it is frequently tolerated by different
protein folds.
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Links
