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Titolo:
Investigation of the mechanism of domain closure in citrate synthase by molecular dynamics simulation
Autore:
Roccatano, D; Mark, AE; Hayward, S;
Indirizzi:
Univ E Anglia, Sch Informat Syst, Royal Soc, Wolfson Bioinformat Lab, Norwich NR2 7TJ, Norfolk, England Univ E Anglia Norwich Norfolk England NR2 7TJ h NR2 7TJ, Norfolk, England Univ Groningen, BIOSON Res Inst, Biophys Chem Lab, Groningen, Netherlands Univ Groningen Groningen Netherlands s Chem Lab, Groningen, Netherlands
Titolo Testata:
JOURNAL OF MOLECULAR BIOLOGY
fascicolo: 5, volume: 310, anno: 2001,
pagine: 1039 - 1053
SICI:
0022-2836(20010727)310:5<1039:IOTMOD>2.0.ZU;2-E
Fonte:
ISI
Lingua:
ENG
Soggetto:
NORMAL-MODE ANALYSIS; COLLECTIVE MOTIONS; PROTEIN DYNAMICS; COENZYME-A; OXALOACETATE; LYSOZYME; SOLVENT; COMPLEX; PATHS; WATER;
Keywords:
hinge bending; hinge axis; dynamic domains; essential dynamics analysis; rigid-body analysis;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
33
Recensione:
Indirizzi per estratti:
Indirizzo: Hayward, S Univ E Anglia, Sch Informat Syst, Royal Soc, Wolfson Bioinformat Lab, Norwich NR2 7TJ, Norfolk, England Univ E Anglia Norwich Norfolk England NR2 7TJ Norfolk, England
Citazione:
D. Roccatano et al., "Investigation of the mechanism of domain closure in citrate synthase by molecular dynamics simulation", J MOL BIOL, 310(5), 2001, pp. 1039-1053

Abstract

Six, 2 ns molecular dynamics simulations have been performed on the homodimeric enzyme citrate synthase. In three, both monomers were started from the open, unliganded X-ray conformation. In the remaining three, both monomers started from a closed, liganded X-ray conformation, with the ligands removed. Projecting the motion from the simulations onto the experimental domain motion revealed that the free-energy profile is rather flat around the open conformation, with steep sides. The most closed conformations correspondto hinge-bending angles of 12-14 degrees compared to the 20 degrees that occurs upon the binding of oxaloacetate. It is also found that the open, unliganded X-ray conformation is situated at the edge of the steep rise in free energy, although conformations that are about 5 degrees more open were sampled. A rigid-body essential dynamics analysis of the combined open trajectories has shown that domain motions in the direction of the closed X-ray conformation are compatible with the natural domain motion of the unligandedprotein, which has just two main degrees of freedom. The simulations starting from the closed conformation suggest a free-energy profile with a smallbarrier in going from the closed to open conformation. A combined essential dynamics and hinge-bending analysis of a trajectory that spontaneously converts from the closed to open state shows an almost exact correspondence to the experimental transition that occurs upon ligand binding. The simulations support the conclusion from an earlier analysis of the experimental transition that the beta -hairpin acts as a mechanical hinge by attaching the small domain to the large domain through a conserved main-chain hydrogen bond and salt-bridges, and allowing rotation to occur via its two flexible termini. The results point to a mechanism of domain closure in citrate synthase that has analogy to the process of closing a door. (C) 2001 Academic Press.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 03/12/20 alle ore 12:02:37