title: 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.
abstract: 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.
authors.affiliation: BioChip Research Center, Hoseo University, Asan 336-795, Republic of Korea.
authors.forename: Youngjin
authors.initials: Y
authors.lastname: Choi
authors.forename: Hyunmyung
authors.initials: H
authors.lastname: Kim
authors.forename: Jong Hyun
authors.initials: JH
authors.lastname: Lee
authors.forename: Sungjun
authors.initials: S
authors.lastname: Park
authors.forename: Karpjoo
authors.initials: K
authors.lastname: Jeong
authors.forename: Seunho
authors.initials: S
authors.lastname: Jung
mesh_terms: D005643:Fucose / Q000378:metabolism*; D006860:Hydrogen Bonding; D019476:Insect Proteins / Q000737:chemistry* / Q000378:metabolism; D056004:Molecular Dynamics Simulation; D010455:Peptides / Q000737:chemistry* / Q000378:metabolism; D011480:Protease Inhibitors / Q000737:chemistry* / Q000378:metabolism; D011489:Protein Denaturation; D017510:Protein Folding; D055550:Protein Stability; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D013696:Temperature; D013997:Time Factors
chemical_list: D019476:Insect Proteins; D010455:Peptides; D011480:Protease Inhibitors; D005643:Fucose