PMID- 20053575
OWN - NLM
STAT- MEDLINE
DCOM- 20100514
LR  - 20171116
IS  - 1873-4243 (Electronic)
IS  - 1093-3263 (Linking)
VI  - 28
IP  - 6
DP  - 2010 Feb 26
TI  - Structural stabilization of a rigid beta-sheet cluster of fucosylated proteinase 
      inhibitor PMPC (Pars intercerebralis major peptide C) against thermal 
      denaturation: An unfolding molecular dynamics simulation study.
PG  - 487-94
LID - 10.1016/j.jmgm.2009.11.003 [doi]
AB  - Unfolding behavior of glycosylated- and unglycosylated proteinase inhibitor Pars 
      intercerebralis major peptide C (PMPC) at 350 K were traced with molecular 
      dynamics simulations using the CHARMM program. The fucosylated PMPC (FPMPC) 
      possesses a nearly identical protein structure with PMPC, differing only by the 
      presence of a single fucose residue linked to Thr9 in the PMPC. Attachment of a 
      monomeric fucose residue to the Thr9 in PMPC resulted in a change of the 
      denaturing process of FPMPC. Simulations showed that the unfolding of PMPC 
      involved significant weakening of non-local interactions whereas fucosylation led 
      FPMPC to preserve the non-local interactions, even in its denatured form. Even in 
      simulations over 16 ns at 350 K, FPMPC remained relatively stable in a less 
      denatured conformation. However, the conformation of PMPC transformed to a fully 
      unfolded state within 5 ns in the simulation at 350 K. This difference was due to 
      the formation of fucose-mediated hydrogen bonds and non-local contacts by the 
      attached fucose residue of FPMPC. In the case of FPMPC, fucosyl residue was 
      involved in maintaining a rigid beta-sheet cluster through interaction with the 
      hydrogen bond network. These high-temperature unfolding MD simulations provide a 
      theoretical basis for a previous experimental work in which FPMPC showed stable 
      unfolding thermodynamics compared to unfucosylated PMPC, suggesting that single 
      fucosylation induces conformational stabilization of PMPC by tertiary contacts.
CI  - Copyright 2009 Elsevier Inc. All rights reserved.
FAU - Choi, Youngjin
AU  - Choi Y
AD  - BioChip Research Center, Hoseo University, Asan 336-795, Republic of Korea.
FAU - Kim, Hyunmyung
AU  - Kim H
FAU - Lee, Jong Hyun
AU  - Lee JH
FAU - Park, Sungjun
AU  - Park S
FAU - Jeong, Karpjoo
AU  - Jeong K
FAU - Jung, Seunho
AU  - Jung S
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20091203
PL  - United States
TA  - J Mol Graph Model
JT  - Journal of molecular graphics & modelling
JID - 9716237
RN  - 0 (Insect Proteins)
RN  - 0 (Peptides)
RN  - 0 (Protease Inhibitors)
RN  - 28RYY2IV3F (Fucose)
SB  - IM
MH  - Fucose/*metabolism
MH  - Hydrogen Bonding
MH  - Insect Proteins/*chemistry/metabolism
MH  - *Molecular Dynamics Simulation
MH  - Peptides/*chemistry/metabolism
MH  - Protease Inhibitors/*chemistry/metabolism
MH  - Protein Denaturation
MH  - *Protein Folding
MH  - Protein Stability
MH  - Protein Structure, Secondary
MH  - Protein Structure, Tertiary
MH  - *Temperature
MH  - Time Factors
EDAT- 2010/01/08 06:00
MHDA- 2010/05/15 06:00
CRDT- 2010/01/08 06:00
PHST- 2009/09/10 00:00 [received]
PHST- 2009/11/20 00:00 [revised]
PHST- 2009/11/24 00:00 [accepted]
PHST- 2010/01/08 06:00 [entrez]
PHST- 2010/01/08 06:00 [pubmed]
PHST- 2010/05/15 06:00 [medline]
AID - S1093-3263(09)00161-2 [pii]
AID - 10.1016/j.jmgm.2009.11.003 [doi]
PST - ppublish
SO  - J Mol Graph Model. 2010 Feb 26;28(6):487-94. doi: 10.1016/j.jmgm.2009.11.003. 
      Epub 2009 Dec 3.