title: Structural and functional conservation profiles of novel cathepsin L-like proteins identified in the Drosophila melanogaster genome.
abstract: Cathepsin L is a cysteine protease which degrades connective tissue proteins including collagen, elastin, and fibronectin. In this study, five well-characterized cathepsin L proteins from different arthropods were used as query sequences for the Drosophila genome database. The search yielded 10 cathepsin L-like sequences, of which eight putatively represent novel cathepsin L-like proteins. To understand the phylogenetic relationship among these cathepsin L-like proteins, a phylogenetic tree was constructed based on their sequences. In addition, models of the tertiary structures of cathepsin L were constructed using homology modeling methods and subjected to molecular dynamics simulations to obtain reasonable structure to understand its dynamical behavior. Our findings demonstrate that all of the potential Drosophila cathepsin L-like proteins contain at least one cathepsin propeptide inhibitor domain. Multiple sequence alignment and homology models clearly highlight the conservation of active site residues, disulfide bonds, and amino acid residues critical for inhibitor binding. Furthermore, comparative modeling indicates that the sequence/structure/function profiles and active site architectures are conserved.
authors.affiliation: a An Autonomous Institute of Department of Biotechnology, Government of India , Institute of Life Sciences , Nalco Square, Bhubaneswar , 751023 , India .
authors.forename: Sunil
authors.initials: S
authors.lastname: Kumar
authors.forename: Rohit
authors.initials: R
authors.lastname: Farmer
authors.forename: Andrew P
authors.initials: AP
authors.lastname: Turnbull
authors.forename: Niraj Kanti
authors.initials: NK
authors.lastname: Tripathy
authors.forename: Babu A
authors.initials: BA
authors.lastname: Manjasetty
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D056668:Cathepsin L / Q000737:chemistry* / Q000145:classification / Q000235:genetics; D017124:Conserved Sequence / Q000235:genetics; D004220:Disulfides / Q000737:chemistry; D029721:Drosophila Proteins / Q000737:chemistry* / Q000145:classification / Q000235:genetics; D004331:Drosophila melanogaster / Q000201:enzymology* / Q000235:genetics; D016678:Genome / Q000235:genetics; D007527:Isoenzymes / Q000737:chemistry / Q000145:classification / Q000235:genetics; D008958:Models, Molecular; D056004:Molecular Dynamics Simulation; D008969:Molecular Sequence Data; D010802:Phylogeny; D017434:Protein Structure, Tertiary; D017386:Sequence Homology, Amino Acid
chemical_list: D004220:Disulfides; D029721:Drosophila Proteins; D007527:Isoenzymes; D056668:Cathepsin L