| histone H4 |
Sb-RES |
histone H4 of L.
infantum has a high degree of identity with the
histone H4 gene of Leishmania tarentolae and a very low degree of identity with the corresponding region
of histone H4 genes from other organisms. H4 synthesis in Leishmania is tightly coupled to DNA replication by a mechanism
operating at the translational level.63 Despite not being directly related to drug resistance, H4 along
with H3, H2A, and H2B, are studied as possible immunization agents
responsible for DNA-based Leishmania immunity in
vaccine development.64
|
| calpain-like cysteine peptidase |
Sb-RES |
calpain-like proteins constitute
a recently discovered family of calcium-dependent cysteine peptidases.65 They have an important role as virulence factors
that modulate the mammalian host’s immune response to Leishmania ssp.54 They are not
reported to be related to drug-resistance phenomena, but their key
role in Trypanosomatid infection makes them candidates for drug discovery.66
|
| Lipase—Class 3 |
Sb-RES |
lipases are esterases able
to hydrolyze long-chain acyl-triglycerides into di- and monoglycerides,
glycerol, and free fatty acids at a water/lipid interface for the
survival and infection of pathogens.67 This
enzyme was not correlated yet to drug resistance but gained interest
in drug discovery of new Leishmania ssp. chemotherapeutic
agents.68
|
| cystathione γ lyase |
Sb-RES |
cystathionine γ-lyase
(or γ-cystathionine, EC:4.4.1.1) breaks down cystathionine into
cysteine, α-ketobutyrate, and ammonia by using pyridoxal phosphate
as prosthetic group. It is employed by the parasite to obtain cysteine
from the host’s blood homocysteine.69
|
| acetyl-coenzyme
A synthetase
(AMP forming) |
MIL-RES |
adenosine monophosphate-forming
acetyl CoA synthetase (AceCS, EC:6.2.1.1) is the key enzyme involved
in the conversion of acetate to acetyl CoA. |
| dimethylargininase |
MIL-RES |
also known as dimethylarginine
dimethylaminohydrolase (DDAH), it converts the hosts’ circulating
Asymmetric dimethylarginine into dimethylamine and citrulline. Little
information is reported in literature apart from its amino acidic
sequences and encoding genes. |
| citrate synthase |
MIL-RES |
citrate synthase (E.C. 2.3.3.1)
is in the mitochondrial matrix of eukaryotes and plays a crucial role
in the Kreb’s Cycle. Indeed, it catalyzes the condensation
of acetyl coenzyme A with oxaloacetate to regenerate citric acid.70 Along with glyoxylate cycle enzymes, it provides
the parasite with ATP needed to replicate by breaking down the host’s
glucose.70
|
| kinesin(s) |
PAR-RES |
kinesins are a large family
of proteins that constitute part of the complex cytoskeletal structure
of the parasite flagellum attachment zone.71 They are highly conserved (KIF superfamily) and are characterized
by an ATPasic site and a microtubule-binding site.72
|
| ribonucleoprotein p18, mitochondrial
precursor |
PAR-RES |
ribonucleoprotein p18 (Rab18)
stands out among a limited set of conserved Rab proteins that can
be traced back to the most recent common ancestor of eukaryotes. Even
though its sequence is known, its precise role in organisms still
must be uncovered.73
|
| trypanothione reductase |
PAR-RES |
trypanothione reductase
(ThyR) is a key enzyme that prevents oxidation of the cytosolic trypanothione
(N1–N8-bis(glutathionyl)-spermidine). It is employed by Leishmania to transfer electrons to the tryparedoxin-peroxidase
couple, which reduces the reactive oxygen species produced by the
host’s macrophages.74 Authors agree
to consider it one of the most promising targets for Leishmania-specific drug design along with trypanothione synthetase (TryS),
and it is also confirmed to be one of the many targets of Sb(III)
complexes in Trypanosoma ssp.35,75
|
| dipeptidyl peptidase 3 |
PAR-RES |
dipeptidyl peptidase 3 is
a member of the M49 peptidase family and is a zinc-dependent metallopeptidase
able to cleave dipeptides from its substrates. It is a key enzyme
for the parasite survival in the vector and host environments, as
it allows to degrade exogenous protein fragments and obtain amino
acids for energy production.76 Its levels
were not related to drug resistance, but due to its detection suitability,
its gene can be a reliable DNA marker to investigate the taxonomy
of Leishmania and help disease surveillance.77
|
