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Enzyme structural network and dynamics

Grant number: 16/22365-9
Support Opportunities:Regular Research Grants
Duration: February 01, 2017 - January 31, 2019
Field of knowledge:Biological Sciences - Biochemistry - Enzymology
Principal Investigator:Sandro Roberto Marana
Grantee:Sandro Roberto Marana
Host Institution: Instituto de Química (IQ). Universidade de São Paulo (USP). São Paulo , SP, Brazil


Protein structures can be represented as an interaction network of amino acid residues, which exhibits high clustering and small world properties. Hence protein structural networks are formed by residue clusters connected through short contact pathways. Indeed, the small world property is determined by a small set of residues called central residues or hubs. Protein structures are also dynamic exhibiting side chains, loops and domains movements over a large time range (ps to s). Actually, dynamics is important for protein function and properties.This projects aims to combine these two views of the protein structure in an experimental approach to determine: 1 - the role of the central residues in the protein dynamics and 2 - the contribution of isolate residue clusters to the protein structural stability. In the approach 1 the structural dynamics (ps - ns) of the Imidazole Glycerol Phosphate Synthase (HisF) from the bacteria Thermatoga maritima will be studied using NMR and R1, R2 and NOE analysis of the 15N spin. Based on that, the HisF structural network will be analyzed along its dynamics and the temporal permanence of the central residues will be evaluated. Following that, permanent central residues will be mutated and the effect on the protein dynamics will be determined by comparing the order parameter S2 from the wild-type and mutant HisF.Next, in the approach 2, considering that the (b/a)4 domains that form the (b/a)8 barrels are thermodynamically stable clusters (subset of a network; domain), mutations will be directed to disrupt a significant fraction of the interactions between those domains of the b-glycosidases GH1 from T. maritima and bglB from Paenebacillus polymyxa. Thus, the analysis of these mutant b-glycosidases may reveal the structural stability of each isolate domain and how they are combined to produce the global stability of those b-glycosidases. (AU)

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Scientific publications (5)
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
SOUZA, VALQUIRIA P.; IKEGAMI, CECILIA M.; ARANTES, GUILHERME M.; MARANA, SANDRO R.. Mutations close to a hub residue affect the distant active site of a GH1 beta-glucosidase. PLoS One, v. 13, n. 6, . (14/19439-5, 16/22365-9)
REIS, ANDRE A. O.; SAYEGH, RAPHAEL S. R.; MARANA, SANDRO R.; ARANTES, GUILHERME M.. Combining Free Energy Simulations and NMR Chemical-Shift Perturbation To Identify Transient Cation-pi Contacts in Proteins. JOURNAL OF CHEMICAL INFORMATION AND MODELING, v. 60, n. 2, p. 890-897, . (18/25952-8, 18/08311-9, 16/24096-5, 12/00543-1, 16/22365-9)
ALMEIDA, VITOR M.; MARANA, SANDRO R.. Optimum temperature may be a misleading parameter in enzyme characterization and application. PLoS One, v. 14, n. 2, . (16/22365-9)
OTSUKA, FELIPE A. M.; CHAGAS, RAFAEL S.; ALMEIDA, VITOR M.; MARANA, SANDRO R.. Homodimerization of a glycoside hydrolase family GH1 beta-glucosidase suggests distinct activity of enzyme different states. Protein Science, v. 29, n. 9, . (18/18537-4, 18/25952-8, 16/22365-9)
ALMEIDA, VITOR M.; FRUTUOSO, MAIRA A.; MARANA, SANDRO R.. Search for independent (beta/alpha)(4) subdomains in a (beta/alpha)(8) barrel beta-glucosidase. PLoS One, v. 13, n. 1, . (14/19439-5, 16/22365-9)

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