Structural dynamics and functional analysis of chitin synthases 5 in a phospholipid bilayer.

is an oomycete responsible for a fish disease called saprolegniosis, which poses an economic and environmental burden on aquaculture production. In , CHS5 of (SpCHS5) contains an N-terminal domain, a catalytic domain of the glycosyltransferase -2 family containing a GT-A fold, and a C-terminal transmembrane domain. No three-dimensional structure of SpCHS5 is reported yet disclosing the structural details of this protein. We have developed a structural model of full-length SpCHS5 and validated it by molecular dynamics simulation technique. From the 1 microsecond simulations, we retrieved the stable RoseTTAFold model SpCHS5 protein to explain characteristics and structural features. Furthermore, from the analysis of the movement of chitin in the protein cavity, we assumed that ARG 482, GLN 527, PHE 529, PHE 530, LEU 540, SER 541, TYR 544, ASN 634, THR 641, TYR 645, THR 641, ASN 772 residues as a main cavity lining site. In SMD analysis, we investigated the opening of the transmembrane cavity required for chitin translocation. The pulling of chitin from the internal cavity to the extracellular region was observed through steered molecular dynamics simulations. A comparison of the initial and final structures of chitin complex showed that there's a transmembrane cavity opening in the simulations. Overall, this present work will help us understand the structural and functional basis of CHS5 and design inhibitors against SpCHS5.Communicated by Ramaswamy H. Sarma.