NMR solution structure of h Par14 reveals similarity to the peptidyl prolyl cis/trans isomerase domain of the mitotic regulator h Pin1 but indicates a different functionality of the protein 1 1Edited by A. Fersht

Sekerina, Elena; Rahfeld, Jens; Müller, Jonathan; Fanghänel, Jörg; Rascher, Christine; Fischer, Gunter; Bayer, Peter

doi:10.1006/jmbi.2000.4013

Cited by 66 publications

(100 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Molecular Modeling-The PrsA PPIase domain structure was modeled based on the NMR structure of hPar14 (Protein Data Bank (PDB) entry 1EQ3) (16). The model was built using Insight II (Accelrys, Inc.).…”

Section: Methodsmentioning

confidence: 99%

“…All Essential for PrsA Function in Vivo-Many parvulins consist of functionally and structurally independent domains (8,13,16,35). In order to identify which regions (or domains) of the PrsA protein are required for protein secretion and viability in B. subtilis, a series of deletion mutations of prsA were constructed, and the mutations were characterized for their effects on in vivo PrsA activity (Fig.…”

Section: The N-terminal C-terminal and Parvulin-like Regions Arementioning

confidence: 99%

“…like domain of B. subtilis PrsA, taking advantage of the known structure of a human parvulin, hPar14 (16,35). The parvulinlike domain of PrsA, which contains 45% identical residues with hPar14, could be modeled to a typical parvulin-type PPIase structure (Fig.…”

Section: The N-terminal C-terminal and Parvulin-like Regions Arementioning

confidence: 99%

“…PPIases of this subfamily are involved in the regulation of mitosis (15), and linked to chromatin remodeling and general transcriptional regulation (5). In the second subfamily the PPIase domain is similar to that of hPar14; the ␣1-helix and the loop that precedes it are several residues shorter than in Pin1 (16). Furthermore, these enzymes have an insertion in the loop between ␣4 and ␤3.…”

mentioning

confidence: 99%

“…It lacks the hPar14-type insertion and the Pin1-type cluster of positively charged residues involved in the binding of phosphoserine and -threonine. Many PPIases of this subfamily are bacterial proteins required for the folding and/or maturation of extracytoplasmic proteins (16,17). The periplasmic SurA and PpiD, which have roles in the assembly of outer membrane proteins (4), belong to this subfamily.…”

mentioning

confidence: 99%

See 4 more Smart Citations

Structure-Function Analysis of PrsA Reveals Roles for the Parvulin-like and Flanking N- and C-terminal Domains in Protein Folding and Secretion in Bacillus subtilis

Vitikainen

Lappalainen

Seppälä

et al. 2004

Journal of Biological Chemistry

118

View full text Add to dashboard Cite

The PrsA protein of Bacillus subtilis is an essential membrane-bound lipoprotein that is assumed to assist post-translocational folding of exported proteins and stabilize them in the compartment between the cytoplasmic membrane and cell wall. This folding activity is consistent with the homology of a segment of PrsA with parvulin-type peptidyl-prolyl cis/trans isomerases (PPIase). In this study, molecular modeling showed that the parvulin-like region can adopt a parvulin-type fold with structurally conserved active site residues. PrsA exhibits PPIase activity in a manner dependent on the parvulin-like domain. We constructed deletion, peptide insertion, and amino acid substitution mutations and demonstrated that the parvulin-like domain as well as flanking N-and C-terminal domains are essential for in vivo PrsA function in protein secretion and growth. Surprisingly, none of the predicted active site residues of the parvulin-like domain was essential for growth and protein secretion, although several active site mutations reduced or abolished the PPIase activity or the ability of PrsA to catalyze proline-limited protein folding in vitro. Our results indicate that PrsA is a PPIase, but the essential role in vivo seems to depend on some non-PPIase activity of both the parvulin-like and flanking domains.

show abstract

Section: Methodsmentioning

confidence: 99%

Section: The N-terminal C-terminal and Parvulin-like Regions Arementioning

confidence: 99%

Section: The N-terminal C-terminal and Parvulin-like Regions Arementioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

See 3 more Smart Citations

Structure-Function Analysis of PrsA Reveals Roles for the Parvulin-like and Flanking N- and C-terminal Domains in Protein Folding and Secretion in Bacillus subtilis

Vitikainen

Lappalainen

Seppälä

et al. 2004

Journal of Biological Chemistry

118

View full text Add to dashboard Cite

show abstract

Peptidyl‐prolylcis/transIsomerases

Fischer

2008

Protein Science Encyclopedia

View full text Add to dashboard Cite

The stereospecificity of peptidyl prolyl cis/trans isomerases (PPIases) was studied using tetrapeptide substrate analogs in which one amino acid residue was replaced by the cognate D-amino acid in various positions of the peptide chain. Reversed stereocenters around proline markedly increased the rate of the spontaneous trans to cis isomerization of the prolyl bond whereas cis to trans isomerizations were less sensitive. PPIases like human cyclophilin18, human FKBP12, Escherichia coli parvulin10 and the PPIase domain of E. coli trigger factor exhibited stereoselectivity demanding at the P I to P P P position of the substrate chain. The discriminating factor for stereoselectiv-ity was the lack of formation of the Michaelis complexes of the diastereomeric substrates. However, D-alanine at the P I position preserved considerable affinity to the active site, and largely prevented activation of the catalytic machinery for all PPIases investigated. z 1998 Federation of European Biochemical Societies.

show abstract

Catalysis of Peptidyl‐prolylcis/transIsomerization by Enzymes

Fischer¹

2005

Protein Folding Handbook

View full text Add to dashboard Cite

NMR solution structure of h Par14 reveals similarity to the peptidyl prolyl cis/trans isomerase domain of the mitotic regulator h Pin1 but indicates a different functionality of the protein 1 1Edited by A. Fersht

Cited by 66 publications

References 34 publications

Structure-Function Analysis of PrsA Reveals Roles for the Parvulin-like and Flanking N- and C-terminal Domains in Protein Folding and Secretion in Bacillus subtilis

Structure-Function Analysis of PrsA Reveals Roles for the Parvulin-like and Flanking N- and C-terminal Domains in Protein Folding and Secretion in Bacillus subtilis

Peptidyl‐prolylcis/transIsomerases

Catalysis of Peptidyl‐prolylcis/transIsomerization by Enzymes

Contact Info

Product

Resources

About