title: Analysis of sequence, structure of GAPDH of Leishmania donovani and its interactions.
abstract: Drug resistance acquired by Leishmania donovani (Ldv) is a major problem in the treatment and control of visceral leishmaniasis (VL). Glyceraldehyde-3-phosphate dehydrogenase (GAPDH), a major glycolytic enzyme has been targeted as is found in other protozoan which cause diseases like sleeping sickness. GAPDH gene of Ldv (AG83 strain) was amplified, sequenced, and modeled on the basis of crystal structure of Leishmania mexicana. The model of the Ldv GAPDH exhibited NAD-binding domain with Rossmann folding. Virtual screening of different experimentally proved compounds with the crystal and the modeled structures of GAPDH of Leishmania strains revealed diverse binding affinities of different compounds. Comparison of binding affinities (based on different programs) of compounds revealed that discovery studio v2.5 (Ligandfit) was able to predict the most hit compounds, the best hit compounds against GAPDH of Leishmania strains are hydrazine, vetrazine, and benzyl carbazate. It is predicted that patients suffering from both VL and cardiac disorders (atrial fibrillation) may benefit if they are treated with warfarin in conjunction with first-line antileishmanial therapies such as miltefosine and AmBisome.
authors: BioMedical Informatics Center, Rajendra Memorial Research Institute of Medical Sciences, Agam Kuan, 800007 Patna, India. ganeshcs@icmr.org.in
authors: Ganesh Chandra
authors: GC
authors: Sahoo
authors: Manas Ranjan
authors: MR
authors: Dikhit
authors: Mukta
authors: M
authors: Rani
authors: Md Yousuf
authors: MY
authors: Ansari
authors: Chanda
authors: C
authors: Jha
authors: Sindhuprava
authors: S
authors: Rana
authors: Pradeep
authors: P
authors: Das
mesh_terms: D000595:Amino Acid Sequence; D001665:Binding Sites; D017931:DNA Primers / Q000378:metabolism; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000737:chemistry* / Q000378:metabolism*; D007893:Leishmania donovani / Q000187:drug effects / Q000201:enzymology*; D062105:Molecular Docking Simulation; D056004:Molecular Dynamics Simulation; D008969:Molecular Sequence Data; D009243:NAD / Q000378:metabolism; D010802:Phylogeny; D011485:Protein Binding / Q000187:drug effects; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D021122:Protein Subunits / Q000737:chemistry / Q000378:metabolism; D016053:RNA, Protozoan / Q000302:isolation & purification; D015203:Reproducibility of Results; D020539:Sequence Analysis, Protein; D013816:Thermodynamics; D014230:Triazoles / Q000737:chemistry / Q000494:pharmacology
chemical_list: D017931:DNA Primers; D021122:Protein Subunits; D016053:RNA, Protozoan; D014230:Triazoles; D009243:NAD; C101425:posaconazole; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases