| Grant number: | 16/22365-9 |
| Support Opportunities: | Regular Research Grants |
| Start date: | February 01, 2017 |
| End date: | 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 |
Abstract
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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