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PDBsum entry 1jns
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Contents |
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* Residue conservation analysis
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References listed in PDB file
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Key reference
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Title
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Solution structure of escherichia coli par10: the prototypic member of the parvulin family of peptidyl-Prolyl cis/trans isomerases.
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Authors
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A.Kühlewein,
G.Voll,
B.Hernandez alvarez,
H.Kessler,
G.Fischer,
J.U.Rahfeld,
G.Gemmecker.
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Ref.
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Protein Sci, 2004,
13,
2378-2387.
[DOI no: ]
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PubMed id
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Abstract
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E. coli Par10 is a peptidyl-prolyl cis/trans isomerase (PPIase) from Escherichia
coli catalyzing the isomerization of Xaa-Pro bonds in oligopeptides with a broad
substrate specificity. The structure of E. coli Par10 has been determined by
multidimensional solution-state NMR spectroscopy based on 1207 conformational
constraints (1067 NOE-derived distances, 42 vicinal coupling-constant
restraints, 30 hydrogen-bond restraints, and 68 phi/psi restraints derived from
the Chemical Shift Index). Simulated-annealing calculations with the program
ARIA and subsequent refinement with XPLOR yielded a set of 18 convergent
structures with an average backbone RMSD from mean atomic coordinates of 0.50 A
within the well-defined secondary structure elements. E. coli Par10 is the
smallest known PPIase so far, with a high catalytic efficiency comparable to
that of FKBPs and cyclophilins. The secondary structure of E. coli Par10
consists of four helical regions and a four-stranded antiparallel beta-sheet.
The N terminus forms a beta-strand, followed by a large stretch comprising three
alpha-helices. A loop region containing a short beta-strand separates these
helices from a fourth alpha-helix. The C terminus consists of two more
beta-strands completing the four-stranded anti-parallel beta-sheet with strand
order 2143. Interestingly, the third beta-strand includes a Gly-Pro cis peptide
bond. The curved beta-strand forms a hydrophobic binding pocket together with
alpha-helix 4, which also contains a number of highly conserved residues. The
three-dimensional structure of Par10 closely resembles that of the human
proteins hPin1 and hPar14 and the plant protein Pin1At, belonging to the same
family of highly homologous proteins.
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Figure 3.
Figure 3. Topology of E. coli Par10. Filled arrows
symbolize experimental H[  ]-H[ ]NOE contacts;
open arrows reflect observed H[N]-H[N] NOEs within the  -sheet.
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Figure 6.
Figure 6. Orientation of the H-bonds in the -sheet and
putative substrate binding site of different Parvulins. (A)
Arrangement of the G75-P76 cis amide bond in E. coli Par10,
compared with the two homologous structures hPin1 and hPar14. In
spite of the bulge resulting from the cis peptide bond, the -sheet of E.
coli Par10 can form all four H-bonds whereas the structures of
hPar14 and hPin1 with trans-Pro are only stabilized by three
H-bonds in this region (figure produced with Insight II, MSI
Inc.). (B) Comparison of the putative binding pockets of hPar14
(PDB code 1eq3, green residues) and hPin1 (PDB code 1pin; red
residues) overlaid on the E. coli Par10 structure (PDB code
1jnt; blue residues, grey backbone). The labeled residues are
highly conserved in all parvulins and may be involved in the
catalytic activity of these parvulins (figure produced with
MOLMOL, version 2k.1; Koradi et al. 1996). (C) Connolly surface
of E. coli Par10. Helix 4 (left) and the curved -sheet form a
lipophilic gap (brown), enabling a lipophilic oligopeptide
substrate to bind (figure produced with the MOLCAD module of the
program Sybyl, version 6.3; Tripos AG).
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The above figures are
reprinted
by permission from the Protein Society:
Protein Sci
(2004,
13,
2378-2387)
copyright 2004.
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