TY - JOUR
T1 - Solution structure of the human parvulin-like peptidyl prolyl cis/trans isomerase, hPar14
AU - Terada, Tohru
AU - Shirouzu, Mikako
AU - Fukumori, Yasuhiro
AU - Fujimori, Fumihiro
AU - Ito, Yutaka
AU - Kigawa, Takanori
AU - Yokoyama, Shigeyuki
AU - Uchida, Takafumi
N1 - Funding Information:
We thank Dr Brian O. Smith for providing the input files for the structure calculation using the ARIA module of the program X-PLOR. This work was supported by Grants-in-Aid from the Ministry of Education, Science, Sports and Culture, Japan. T. T. was supported by Research Fellowships of the Japan Society for the Promotion of Science for Young Scientists. Molecular graphic images were produced using the MidasPlus software from the Computer Graphics Laboratory, University of California, San Francisco.
PY - 2001/1/26
Y1 - 2001/1/26
N2 - The hPar14 protein is a peptidyl prolyl cis/trans isomerase and is a human parvulin homologue. The hPar14 protein shows about 30% sequence identity with the other human parvulin homologue, hPin1. Here, the solution structure of hPar14 was determined by nuclear magnetic resonance spectroscopy. The N-terminal 35 residues preceding the peptidyl prolyl isomerase domain of hPar14 are unstructured, whereas hPin1 possesses the WW domain at its N terminus. The fold of residues 36-131 of hPar14, which comprises a four-stranded β-sheet and three α-helices, is superimposable onto that of the peptidyl prolyl isomerase domain of hPin1. To investigate the interaction of hPar14 with a substrate, the backbone chemical-shift changes of hPar14 were monitored during titration with a tetra peptide. Met90, Val91, and Phe94 around the N terminus of α3 showed large chemical-shift changes. These residues form a hydrophobic patch on the molecular surface of hPar14. Two of these residues are conserved and have been shown to interact with the proline residue of the substrate in hPin1. On the other hand, hPar14 lacks the hPin1 positively charged residues (Lys63, Arg68, and Arg69), which determine the substrate specificity of hPin1 by interacting with phosphorylated Ser or Thr preceding the substrate Pro, and exhibits a different structure in the corresponding region. Therefore, the mechanism determining the substrate specificity seems to be different between hPar14 and hPin1.
AB - The hPar14 protein is a peptidyl prolyl cis/trans isomerase and is a human parvulin homologue. The hPar14 protein shows about 30% sequence identity with the other human parvulin homologue, hPin1. Here, the solution structure of hPar14 was determined by nuclear magnetic resonance spectroscopy. The N-terminal 35 residues preceding the peptidyl prolyl isomerase domain of hPar14 are unstructured, whereas hPin1 possesses the WW domain at its N terminus. The fold of residues 36-131 of hPar14, which comprises a four-stranded β-sheet and three α-helices, is superimposable onto that of the peptidyl prolyl isomerase domain of hPin1. To investigate the interaction of hPar14 with a substrate, the backbone chemical-shift changes of hPar14 were monitored during titration with a tetra peptide. Met90, Val91, and Phe94 around the N terminus of α3 showed large chemical-shift changes. These residues form a hydrophobic patch on the molecular surface of hPar14. Two of these residues are conserved and have been shown to interact with the proline residue of the substrate in hPin1. On the other hand, hPar14 lacks the hPin1 positively charged residues (Lys63, Arg68, and Arg69), which determine the substrate specificity of hPin1 by interacting with phosphorylated Ser or Thr preceding the substrate Pro, and exhibits a different structure in the corresponding region. Therefore, the mechanism determining the substrate specificity seems to be different between hPar14 and hPin1.
KW - Nuclear magnetic resonance
KW - Peptidyl prolyl cis/trans isomerase
KW - Solution structure
KW - hPar14
KW - hPin1
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U2 - 10.1006/jmbi.2000.4293
DO - 10.1006/jmbi.2000.4293
M3 - Article
C2 - 11162102
AN - SCOPUS:0035951290
VL - 305
SP - 917
EP - 926
JO - Journal of Molecular Biology
JF - Journal of Molecular Biology
SN - 0022-2836
IS - 4
ER -