6VDG

Crystal Structure of the Y182A HisF Mutant from Thermotoga maritima

Summary for 6VDG

• Entry DOI: 10.2210/pdb6vdg/pdb
• Descriptor: Imidazole glycerol phosphate synthase subunit HisF, PHOSPHATE ION (3 entities in total)
• Functional Keywords: cyclase, histidine pathway, tim-barrel, lyase
• Biological source: Thermotoga maritima
• Total number of polymer chains: 1
• Total formula weight: 27742.72

Authors

Almeida, V.M.,Matsuyama, B.Y.,Farah, C.S.,Marana, S.R. (deposition date: 2019-12-27, release date: 2020-01-15, Last modification date: 2023-10-11)

Primary citation

Medeiros Almeida, V.,Chaudhuri, A.,Cangussu Cardoso, M.V.,Matsuyama, B.Y.,Monteiro Ferreira, G.,Goulart Trossini, G.H.,Salinas, R.K.,Loria, J.P.,Marana, S.R.
Role of a high centrality residue in protein dynamics and thermal stability.
J.Struct.Biol., 213:107773-107773, 2021

PubMed Abstract: Centralities determined from Residue Interaction Networks (RIN) in proteins have been used to predict aspects of their structure and dynamics. Here, we correlate the Eigenvector Centrality (E) with the rate constant for thermal denaturation (k) of the HisF protein from Thermotoga maritima based on 12 single alanine substitution mutants. The molecular basis for this correlation was further explored by studying a mutant containing a replacement of a high E residue, Y182A, which displayed increased k at 80 °C. The crystallographic structure of this mutant showed few changes, mostly in two flexible loops. The H-N -HSQC showed only subtle changes of cross peak positions for residues located near the mutation site and scattered throughout the structure. However, the comparison of the RIN showed that Y182 is the vertex of a set of high centrality residues that spreads throughout the HisF structure, which is lacking in the mutant. Cross-correlation displacements of Cα calculated from a molecular dynamics simulation at different temperatures showed that the Y182A mutation reduced the correlated movements in the HisF structure above 70 °C. H-N NMR chemical shift covariance using temperature as perturbation were consistent with these results. In conclusion the increase in temperature drives the structure of the mutant HisF-Y182A into a less connected state, richer in non-concerted motions, located predominantly in the C-terminal half of the protein where Y182 is placed. Conversely, wild-type HisF responds to increased temperature as a single unit. Hence the replacement of a high E residue alters the distribution of thermal energy through HisF structure.

PubMed: 34320379
DOI: 10.1016/j.jsb.2021.107773

Experimental method

X-RAY DIFFRACTION (2.79 Å)