SLAS Discovery - Special Issue on Advances in MALDI Mass Spectrometry for Drug Discovery - Volume 22 Issue 10 - December 2017 - 1233

1233

Sharma and Bisht
Table 3. 3D Modeling and Docking Parameters Used for Bioinformatic Analysis.
Attractive Repulsive
Vander wall Vander wall
Forces
Forces

TM
Score

RMSD
Value, Å

Drug

Global
Energy

Rv1860

0.28 ± 0.09

16.7 ± 2.9

SM

-68.20

-24.82

5.35

Rv1980c

0.66 ± 0.13

6.5 ± 4.0

SM

-40.70

-17.19

3.97

Rv2140c

0.97 ± 0.05

1.7 ± 1.4

SM

-46.22

-21.00

9.79

Rv1636

0.80 ± 0.09

3.4 ± 2.4

SM

-34.18

-16.48

6.49

Rv1926c

0.64 ± 0.13

6.1 ± 3.7

SM

-40.02

-18.78

4.70

ORF No.

ACE

Interacting
Amino Acids

Remarks

-22.40 18, 51-56, 67, SM binds to the
69, 90-93,
fibronectin
103, and 138
attachment domain
of alanine- and
proline-rich
secreted protein
-12.41 66, 69, 130-132, SM binds to the
144, 147, 148, domain of
190, 199, and
unknown function
201
DUF3298 of the
immunogenic
protein MPT64
-16.46 4-9, 10, 11, 67, SM binds to the
69-71, 75, 78, PEBP domain of
and 131
the hypothetical
UPF0098 protein
-12.22 11-13, 39,
SM binds to the
41-42, 44, 58, conserved
59 62, 63, 65, USP-A domain of
66, and 69
uncharacterized
protein
-11.18 12, 13, 19, 22, SM binds to the
43, 45, 47, 48, domain of
50, 52, 89-92, unknown function
94, 95, 149,
DUF1942 of the
151, and 154
immunogenic
protein MPT63

ACE, atomic contact energy; ORF, open reading frame; PEBP, phosphatidylethanolamine binding protein; RMSD, root mean square deviation; SM,
streptomycin; TM, TM score, template modeling score; USP-A, universal stress protein A.

Rv1980c, and Rv1926c belonged to cell wall and cell processes; and Rv3804c, Rv0009, and Rv2140c belonged to lipid
metabolism, information pathways, and conserved hypothetical categories, respectively.
Rv0350 and Rv0440 are the 70-kDa and 60-kDa chaperone proteins respectively involved in refolding as well as
proper assembly of unfolded/misfolded polypeptides under
stresses. Rv0350 has a peptide binding domain as well as
ATPase domain, which regulates the overexpression of
other heat shock proteins.28 Rv0440 is the second copy of
60-kDa chaperonin in the M. tuberculosis genome, which is
situated far away from the classic GroEL-Cpn10 operon
and suggests a specialized regulation in M. tuberculosis.29
Sharma et al.8 reported that these were overexpressed in
SM-resistant M. tuberculosis. Overexpression of these
might mitigate the toxicity by maintaining the proper folding of unfolded/misfolded protein or truncated proteins.
Rv3846, identified as superoxide dismutase, destroys
free radicals that are normally produced within the cells
under oxidative stress. Superoxide detoxifying enzyme,
SodA (Rv3846), together with the thiol-oxidoreductase and

an integral membrane protein, DoxX (Rv3005c), form a
membrane-associated oxidoreductase complex (MRC).
Loss of any MRC component is correlated with defective
recycling of mycothiol, which is a functional analogue of
glutathione in M. tuberculosis.30 In the present study, overexpression of Rv3846 might protect M. tuberculosis cellular damage by mitigating the toxicity and lead to drug
resistance.
Rv3804c has been identified as diacylglycerol acyltransferase/mycolyltransferase, which is involved in cell wall
mycoloylation. It possesses a mycolyltransferase activity
required for the biogenesis of trehalose dimycolate (cord
factor) and maintaining cell wall integrity, which leads to
persistent tuberculosis infection.31 In our study, overexpression of Rv3804c might be protect the M. tuberculosis to
persist leads to development of streptomycin resistance.
Rv0815c is the putative thiosulfate sulfurtransferase
(Rhodanese-like protein) involved in the formation of thiosulfate and probably protects the becillai from oxidative stress.
Singhal et al.32 reported that Rv0815c was overexpressed
intraphagosomally in THP-1 cells infected by a drug-resistant
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