03485nas a2200445   4500000000100000008004100001260001300042653002400055653002300079653002600102653001100128653001200139653002200151653002200173653002200195653002800217653002500245653002200270653003100292653002000323653002500343653001500368653002100383100001500404700001500419700001200434700001600446700001300462700001200475700002400487700001400511700001800525700001600543700001600559245014700575300000900722490000600731520228800737022001403025       2004                            d  c2004 Mar10aAmino Acid Sequence10aBacterial Proteins10aComputational Biology10aHumans10aleprosy10aMembrane Proteins10aModels, Molecular10aMolecular Mimicry10aMolecular Sequence Data10aMycobacterium leprae10aMyelin P0 Protein10aNeurodegenerative Diseases10aProtein Binding10aProtein Conformation10aProteomics10aReceptors, Virus1 aVardhini D1 aSuneetha S1 aAhmed N1 aJoshi D S M1 aKaruna S1 aMagee X1 aVijayalakshmi D S R1 aSridhar V1 aKarunakar K V1 aArchelos JJ1 aSuneetha LM00aComparative proteomics of the Mycobacterium leprae binding protein myelin P0: its implication in leprosy and other neurodegenerative diseases.  a21-80 v43 a<p>Mycobacterium leprae, the causative agent of leprosy invades Schwann cells of the peripheral nerves leading to nerve damage and disfigurement, which is the hallmark of the disease. Wet experiments have shown that M. leprae binds to a major peripheral nerve protein, the myelin P zero (P0). This protein is specific to peripheral nerve and may be important in the initial step of M. leprae binding and invasion of Schwann cells which is the feature of leprosy. Though the receptors on Schawann cells, cytokines, chemokines and antibodies to M. leprae have been identified the molecular mechanism of nerve damage and neurodegeneration is not clearly defined. Recently pathogen and host protein/nucleotide sequence similarities (molecular mimicry) have been implicated in neurodegenerative diseases. The approach of the present study is to utilise bioinformatic tools to understand leprosy nerve damage by carrying out sequence and structural similarity searches of myelin P0 with leproma and other genomic database. Since myelin P0 is unique to peripheral nerve, its sequence and structural similarities in other neuropathogens have also been noted. Comparison of myelin P0 with the M. leprae proteins revealed two characterised proteins, Ferrodoxin NADP reductase and a conserved membrane protein, which showed similarity to the query sequence. Comparison with the entire genomic database (www.ncbi.nlm.nih.gov) by basic local alignment search tool for proteins (BLASTP) and fold classification of structure-structure alignment of proteins (FSSP) searches revealed that myelin P0 had sequence/structural similarities to the poliovirus receptor, coxsackie-adenovirus receptor, anthrax protective antigen, diphtheria toxin, herpes simplex virus, HIV gag-1 peptide, and gp120 among others. These proteins are known to be associated directly or indirectly with neruodegeneration. Sequence and structural similarities to the immunoglobin regions of myelin P0 could have implications in host-pathogen interactions, as it has homophilic adhesive properties. Although these observed similarities are not highly significant in their percentage identity, they could be functionally important in molecular mimicry, receptor binding and cell signaling events involved in neurodegeneration.</p>  a1567-1348