Identification and structure solution of fragment hits against kinetoplastid N -myristoyltransferase

2022

Preprint

We report on the state of the art of research on proteins recognized as potential targets for the development of Leishmania treatments and the search of active chemical species. We have reviewed information from experimental in vitro, in vivo, or in silico sources. We classify the gathered information on: a) vector taxonomy and geographical distribution, b) parasite taxonomy, geographical distribution, c) enzymatic function of proteins related to the parasite/host in any of its development states, id. est., oxidoreductases, transferases, hydrolases, lyases, isomerases, ligases and cytokines, and d) information on standard and non-standard treatments from bioactive chemical species. Our aim is to provide a much needed reference layout for research efforts aimed to understand the interaction mechanisms of ligand-protein activation/inactivation processes, specifically related to Leishmania, thus, we focus on enzymes known to be part of the biochemical molecular pathways initiated following a Leishmania infectious episode.

Section: Transferases Group (Ec 2)mentioning

confidence: 99%

Section: Transferases Group (Ec 2)mentioning

confidence: 99%

Leishmania Proteomics: An in Silico Perspective

Padilla¹,

Álvarez²,

2022

Preprint

“…79 Modifications with myristate, know as myristoylation, have been implicated in targeting protein to membrane locations, stabilizing protein structures, mediating protein-protein interactions and substrate activation. 79,80 Proteins that are destined to become myristoylated begin its pri- homoeostasis and providing defence against oxidative stress in Leishmania parasites. [84][85][86] The Trypanothione biosynthesis process, indirectly depend on the availability of cysteine and cysteine de novo biosynthesis pathway depend of Serine Acetyltyltransferase and Cysteine Synthase (PDB ID: 4AIR) proteins.…”

Section: Oxidoreductases (Ec 1)mentioning

confidence: 99%

“…mary sequence with the Methionine-Glycine (Met-Gly) sequence group, where Met-amino acid is removed by methionine amino-peptidase protein and myristate molecule is linked via an amide bond 79. N-myristoyltransferase (NMT) protein (PDB ID: 4UCM) catalyzes the co-translational transfer of myristic acid (myristate) from myristoyl-CoA to the N-terminal glycine 80,81. 4UCM is important protein by Leishmania parasites, and this protein is a potential drug target 82.…”

mentioning

confidence: 99%

Leishmania Proteomics: An in Silico Perspective

Padilla¹,

Álvarez²,

2020

Preprint

We report on the state of the art of scientific literature about proteins recognized as potential targets for the development of Leishmania treatments through the search of biologically active chemical species, either from experimental in vitro, in vivo, or in silico sources. We classify the gathered information, in several ways: vector taxonomy and geographical distribution, parasite taxonomic and geographical distribution and enzymatic function (oxidoreductases, transferases, hydrolases, lyases, isomerases, ligases and cytokines). Our aim is to provide a much needed reference layout for research efforts aimed to understand the underpinning physical interactions in ligand-protein activation/inactivation processes. In the specific case of Leishmania, we focus on enzymes known to be part of the biochemical molecular processes initiated following a Leishmania infectious episode.

“…Modifications have been implicated in localization and/or substrate activation. 55 OMP decarboxylase (PDB ID: 3QW3) and UMP synthase (PDB ID:…”

Section: Oxidoreductases (Ec 1)mentioning

confidence: 99%

Leishmania Proteomics: An in Silico Perspective

Ca¹,

Mj²,

2019

Preprint

We report on the state of the art of proteins recognized as potential targets for the development of leishmania treatments through the search of biologically active chemical species, either from experimental in vitro, in vivo, or in silico sources.  We classify the gathered information, in several ways: vector taxonomy and geographical distribution, leishmania parasite taxonomic and geographical distribution and enzymatic function (oxidoreductases, transferases, hydrolases, lyases, isomerases, ligases and cytokines). Our aim is to provide a much needed reference layout for research efforts aimed to understand the background of ligand-protein activation/inactivation processes, in this specific case, related with enzymes known to be part of biochemical cascade reactions initiated following a leishmania infectious episode.