Synthesis and biological investigation of pyrimido 1,2 a 1,3,5 triazine and its analogues 2

Table XVIII Retrieval of top targets of 149b by 3 approaches:
Pharm

S.No

Target name

Function

PDB ids

Mapper
(fit

Reverse
Screen
3d score

score)

1

Epidermal growth factor
receptor

2

Heat shock protein HSP
90-alpha

3

4

144

Cathepsin K

Purine nucleoside
phosphorylase

Cell-surface receptor for members of the
epidermal growth factor family (EGF-family) of
extracellular protein ligands

3lzb, 2qlq

3.751

0.4365

2xdx,1uyk,
1uyh,1uy6,
1uyg

3.749

0.5652

Closely involved in osteoclastic bone resorption
and may participate partially in the disorder of

bone remodeling.

1tu6, 3kx1

3.593

0.5714

Nucleotide transport and metabolism

1a9t, 1lv8,
1pr4, 1ovg,
1vmk, 2qpl,
1z36, 1rfg,
1k9s, 3iom,

3.473

0.9375

Molecular chaperone. Has ATPase activity (By
similarity)


1odj
5

Leukotriene A-4 hydrolase

Hydrolyzes an epoxide moiety of leukotriene A4

(LTA-4) to form leukotriene B4 (LTB-4).

1gw6, 3fum

3.413

0.4483

6

Corticosteroid 11-betadehydrogenase isozyme 1

Catalyzes reversibly the conversion of cortisol to
the inactive metabolite cortisone.

3czr, 3czr,
3d5q

3.205

0.4412

7

Aspartate aminotransferase

Amino acid transport and metabolism

1c9c, 2z9v,

3.131

0.6842

Nucleotide transport and metabolism

1tls,1j3j,
1tlc, 3jsu,
2blc, 3clb,
3k2h, 2aaz,
1sej, 1ju6,
1qzf, 1f28,
1jtq, 1f4d,

3.131

0.5

3.041

0.4667

8

Thymidylate synthase

9

Mitogen-activated protein
kinase 14

Involved in MAP kinase activity

3e92, 3fc1,
1ouy,3new,
3fl4, 1w82

10

Proto-oncogene tyrosineprotein kinase Src

implicated in the pathogenesis of chronic
myelogenous leukemia

1o4r, 2h8h,
3g6g, 3f3t,
1o4i, 1o47

3.024

0.4324

Androgen receptor

Steroid hormone receptors are ligand-activated
transcription factors that regulate eukaryotic gene
expression and affect cellular proliferation.

1z95, 2ax8,
2piq, 3b66

2.994

0.281

11

145


12

Dihydroorotate
dehydrogenase,
mitochondrial

Nucleotide transport and metabolism

2fpy, 1d3h,
2prl, 1tv5,
3i6r

3.405

0.5

13

Cell division protein kinase
2

Involved in protein kinase activity

1p2a, 3eoc,
2v22, 1vop

2.979

0.36111

14

Serine/threonine-protein
kinase Chk1

Required for checkpoint mediated cell cycle
arrest in response to DNA damage or the
presence of unreplicated DNA. May also
negatively regulate cell cycle progression.
Recognizes the substrate consensus sequence [RX-X- S/T]

2ayp, 2e9p,
2e9u,

2.969

0.4375

15

Enoyl-[acyl-carrierprotein] reductase [NADH]

Lipid transport and metabolism

1bvr, 1d8a,
3fng, 1jvf,
3fne

2.963

0.3871

1nhu, 2f9v,
1yvx, 1nhv,
2a4g, 2pxa

2.942

0.3333

16

-

17

Tyrosine-protein
phosphatase non-receptor
type 1

May play an important role in CKII- and p60csrc-induced signal transduction cascades

1no6, 1nny,
3o5x, 1c85,
2shp

2.936

0.2917

18

146

HCV RNA polymerase

Dipeptidyl peptidase 4

Removes N-terminal dipeptides sequentially
from polypeptides having unsubstituted N-

1rwq, 2gbi,
2iit, 1rwq,

2.931

0.5667


termini provided that the penultimate residue is

proline. Plays a role in T-cell activation

2aj8

19

2-C-methyl-D-erythritol
2,4-cyclodiphosphate
synthase

phosphorus-oxygen lyase participates in
biosynthesis of steroids.

1h48, 3ke1

2.927

0.3636

20

Retinoic acid receptor
RXR-beta

Nuclear hormone receptor. Involved in the
retinoic acid response pathway. Binds 9-cis
retinoic acid (9C-RA).

1h9u

2.923

0.4687

Phospholipase A2 KPA2

Involved in phospholipase A2 activity which
cleaves glycerophospholipids to release fatty
acids and lysophospholipids

1po8, 1db5,
1fv0, 1rgb,
1qll, 1oxr,
3l30, 3fo7,
3l69,

2.932

0.65

22

E3 ubiquitin-protein ligase
Mdm2

MDM2, a p53-specific E3 ubiquitin ligase, is the
principal cellular antagonist of p53, acting to
limit the p53 growth-suppressive function in
unstressed cells.

1ttv

2.918

0.4166

23

Collagenase 3

Degrades collagen type I. Does not act on gelatin
or casein. Could have a role in tumoral process.

1xud, 3kek

2.916

0.359

24

Macrophage
metalloelastase

Human Macrophage Metalloelastase Correlates
with Angiogenesis and Prognosis of Gastric
Carcinoma.

1ros

2.915

0.375

21

147


25

3-hydroxy-3methylglutaryl-coenzyme
A reductase

This transmembrane glycoprotein is the ratelimiting enzyme of sterol biosynthesis.

2q1l, 3cd0,
3cd7, 3cd5,
3cct

2.979

0.3

26

Probable uracil
phosphoribosyltransferase

Nucleotide transport and metabolism

1xtu, 1vst.

2.895

0.333

27

2-amino-4-hydroxy-6hydroxymethyldihydropteri
dine pyrophosphokinase

Coenzyme transport and metabolism

1q0n, 3ip0.

2.892

0.619

28

Matrix metalloproteinase-9

May play an essential role in local proteolysis of
the extracellular matrix and in leukocyte
migration.

1gkd, 2ovx,
2ozr

2.879

0.35

29

3-oxoacyl-[acyl-carrierprotein] synthase 3

Lipid transport and metabolism

1u6s, 3il6

2.877

0.325

Involved in RNA binding,

2gpq, 2idv,
1ap8, 2wmc,
1ipb, 1wkw,
3hxg

2.855

0.4412

2.852

0.3409

30

Eukaryotic translation
initiation factor 4E

Phosphorylates and activates not only

148

3-phosphoinositidedependent protein kinase 1

PKB/AKT, but also PKA, PKC-zeta, RPS6KA1

3nax, 2v4l,

and RPS6KB1. May play a general role in

3oaw, 3ml8,

signaling processes and in development.

31

1uu3, 2xck,

3dpd, 3ml9

1e7v, 2chz,
2chx, 2chw,
1e8x, 3ls8
32

Signal recognition particle
protein

Intracellular trafficking, secretion, and vesicular
transport

1o87, 2c03

2.851

0.3714

33

Scytalone dehydratase

Involved in hydro-lyase activity

7std, 6std,
5std

3.835

0.5

34

Pantothenate synthetase

Coenzyme transport and metabolism

1n2h, 3ivc

3.106

0.4571

35

UDP-glucose 4-epimerase

Cell wall/membrane/envelope biogenesis

1lrj, 1lrl,
1ek6

2.98

0.2885

36

Nicotinate-nucleotidedimethylbenzimidazolepho
sphoribosyltransferase

-

1l5l, 1l5m

2.966

0.888

2.992

0.491

2.908

0.5517

Motor protein required for establishing a bipolar
37

Kinesin like protein kif11

spindle. Blocking of KIF11 prevents centrosome
migration and arrest cells in mitosis.

38

Lactoylglutathione lyase

Catalyzes the conversion of hemimercaptal,
formed from methylglyoxal and glutathione, to

149

3k5e, 2gm1,
2uym, 3cjo

1fro, 2za0


S-lactoylglutathione.
Hepatocyte growth factor
receptor

Involved in hepatocyte growth factor activity

3cd8, 3c1x

2.901

0.3478

Transthyretin

Thyroid hormone-binding protein. Probably
transports thyroxine from the bloodstream to the
brain.

1rlb, 2f8i,
3ng5, 3ipe

2.893

0.5357

41

TGF-beta receptor type-1

On ligand binding, forms a receptor complex
consisting of two type II and two type I
transmembrane serine/threonine kinases. It then
bind and activate SMAD transcriptional
complex, enters the nucleus where it binds
transcription cofactors and causes the
transcription of DNA.

1rw8, 2wot

2.879

0.3902

42

Methionine
aminopeptidase

Translation, ribosomal structure and biogenesis

2ea2, 1boa,

2gg8, 2p98,
2g6p

2.948

0.5862

43

1-aminocyclopropane-1carboxylate deaminase

Amino acid transport and metabolism

1j0e, 1j0b

2.867

0.5

44

Cell division protein kinase
2

Involved in protein kinase activity

2vtp, 3eoc

2.853

0.4444

39

40

150


Table XIX Retrieval of top targets of 149f by 3 different VS approaches

Pharm
S No.

Protein name (target name)

Function

PDB ids

Reverse

Mapper
(fit

Screen 3d

score)

score

1s59, 1mn9

3.907

0.2703

1lv8, 1ovg,
1rfg, 1odj,
3iom, 2ai1

4.23

0.52

3.569

0.3429

3.397

0.2917

enzymes that catalyze the exchange of
1

Nucleoside diphosphate
kinase

phosphate groups between different

nucleoside diphosphates

2

Purine nucleoside
phosphorylase

Nucleotide transport and metabolism

3

Phosphoenolpyruvate
carboxykinase, cytosolic
[GTP]

Energy production and conversion

1m51, 1nhx
1khb
1lrj, 1hzj

4

UDP-glucose 4-epimerase

Cell wall/membrane/envelope biogenesis

2p5y, 2c20,
3ehe, 3enk

151


5

Hypothetical protein

-

1vhn, 2q6i,
3kyf, 3kyg,
1ofu, 2e87,
2yqz, 2hek,
2ogi, 1yre,
2d1y, 1p0h,
1q6y, 2gf6

3.358

0.2799

3.197

0.2906

1emd, 3i0p,
1emd, 1hex,
1o6z, 1ur5,
3gvh, 1b8v,
1bmd, 1z2i,

2dfd, 2x0i,
1guz, 1gv0

3.141

0.2653

1jmf, 1tlc,
1b02

3.132

0.522

3.082

0.6163

1nqu, 2c9b,
6

6,7-dimethyl-8ribityllumazine synthase

Coenzyme transport and metabolism

1t13, 2f59,
2obx, 1nqu,
1kyy

7

8

Thymidylate synthase

Nucleotide transport and metabolism

9

152

Malate dehydrogenase

enzyme in the citric acid cycle that
catalyzes the conversion of malate into
oxaloacetate

Imidazole glycerol phosphate
synthase

1ox6, 1ox5
-


This transmembrane glycoprotein is
involved in the control of cholesterol
biosynthesis. It is the rate-limiting enzyme
of sterol biosynthesis.

10

3-hydroxy-3-methylglutarylcoenzyme A reductase

Heat shock protein HSP 90alpha

Molecular chaperone. Has ATPase

11

Cell division protein kinase 2

Involved in protein kinase activity

12

activity (By similarity)

2q1l, 3cd7,
3ccw, 1qax,
3cd5, 1dqa,
1r31

2.991

0.2991

1uyg, 3hz5

2.989

0.3737

2.97

0.4242

2.963

0.4938

2.959

0.3288

2.932

0.3871

1p2a, lke9,
2bts, 2wih
1jvf, 1d8a,

13

Enoyl-[acyl-carrier-protein]
reductase [NADH]

Lipid transport and metabolism

3gr6, 3oig,

1qsg, 2h7i,
2h9i, 2pd4

Has a tyrosine-protein kinase activity. The
VEGF-kinase ligand/receptor signaling
14

Vascular endothelial growth
factor receptor 2

system plays a key role in vascular
development and regulation of vascular

2oh4, 1ywn,
3c7q, 3c7q

permeability.
15

153

2-C-methyl-D-erythritol 2,4cyclodiphosphate synthase

-

1h48, 3ke1,


3q8h
Involved in the activation cascade of

caspases; responsible for apoptosis
16

Caspase-3

execution. It proteolytically cleaves

1rhj, 3kjf

2.926

0.2449

2.905

0.3513

2zb1, 1bmk

2.9

0.3211

1o4r, 3el8

3.157

0.2201

poly(ADP-ribose) polymerase (PARP) at

a 216-Asp- residue
Cell cycle control, cell division,

17

Cell division protein ftsZ
homolog 1

18

Mitogen-activated protein
kinase 14

Involved in MAP kinase activity

Proto-oncogene tyrosineprotein kinase Src

implicated in the pathogenesis of chronic

19

20

Nicotinate-nucleotidedimethylbenzimidazole
phosphoribosyltransferase

ribazole, which is a key component of the

Phosphopantetheine
adenylyltransferase

-

21

154

chromosome partitioning

myelogenous leukemia

1w5e, 1w58

plays a central role in the synthesis of α1l5l, 1l5m

3.12
0.3667

lower ligand of cobalamin
1b6t, 1vlh

3.032

0.2133


Involved in aspartic-type signal peptidase
22

Beta-secretase 1

activity

1xs7, 2wf0

2.981

0.2127

Table XX Retrieval of top targets of 173b by the ReverseScreen 2D and 3D Methods, PharmMapper and Binding DB

S. No.

Protein name (target
name)

Pharm
PDB ids

Mapper (fit

Screen 3d

score)*

Function

Reverse

score*

Adenylate cyclase
type 2

Signal transduction mechanisms

1ab8

3.775

0.4195

2

Vascular endothelial
growth factor receptor
2

Has a tyrosine-protein kinase activity. The
VEGF-kinase ligand/receptor signaling
system plays a key role in vascular
development and regulation of vascular
permeability.

3dtw, 3cpc,
1ywn, 3be2,
3cpb, 3oh4,
3ewh, 1y69,
3c7q

3.6967

0.41

3

Tyrosine-protein
kinase SYK

Positive effector of B-cell antigen receptor
-stimulated responses.

1xbb, 3fqh

2.927

0.52

Androgen receptor

Steroid hormone receptors are ligandactivated transcription factors that regulate
eukaryotic gene expression and affect
cellular proliferation.

1gs4, 3b67,
3b68, 1t7t,
1i37, 2piq,
3b68

3.541

0.73

1

4

155


5

May play an essential role in local
proteolysis of the extracellular matrix and
in leukocyte migration.

1gkc, 2ovx

3.362

0.39

6

2-C-methyl-Derythritol 2,4cyclodiphosphate
synthase

-

1knj, 3ke1,

3.276

0.45

7

Hepatocyte growth
factor receptor

Involved in hepatocyte growth factor
activity

3f82, 3f82,
3cd8, 3clx

3.23

0.49

8

Serine/threonineprotein phosphatase
PP1-gamma catalytic
subunit

Signal transduction mechanisms

1it6, 1u32

3.079

0.2369

9

Enoyl-[acyl-carrierprotein] reductase
[NADH]

Lipid transport and metabolism

2.99

0.254

10

2-amino-4-hydroxy-6hydroxymethyl
dihydropteridine
pyrophosphokinase

Coenzyme transport and metabolism

1cbk, 1ex8

3.129

0.15

11

156

Matrix
metalloproteinase-9

Purine nucleoside
phosphorylase

Nucleotide transport and metabolism

2ai1, 1a9t,

3.036

0.68

1ovg, 1z36,


1z37, 1a9p,
1rfg, 3iom,
1k9s, 1odj,
1rhw, 2ac7,
2ai1

12

13

14

15

157

Serine/threonineprotein kinase Chk1

Required for checkpoint mediated cell
cycle arrest in response to DNA damage or
the presence of unreplicated DNA. May
also negatively regulate cell cycle
progression during unperturbed cell cycles.
Recognizes the substrate consensus
sequence [R-X-X- S/T].

2bro, 2c3k,
3jvr, 2e9p,

3.011

0.44

2.993

0.43

2.974

0.4

2.956

0.2956

2e9u

3el7, 3g6h,

Proto-oncogene
tyrosine-protein kinase
Src

-

Kinesin-like protein
KIF11

Motor protein required for establishing a
bipolar spindle. Blocking of KIF11
prevents centrosome migration and arrest
cells in mitosis with monoastral
microtubule arrays.

Caspase 1

Apoptosis marker

2h8h, 3f3t,
2qq7, 1o4r

3k5e, 2gm1,
2uym, 3cjo,
2fme
1ice


3-hydroxy-3methylglutarylcoenzyme A reductase

This transmembrane glycoprotein is
involved in the control of cholesterol
biosynthesis. It is the rate-limiting enzyme
of sterol biosynthesis.

1hw8, 3cct,

2-amino-4-hydroxy-6hydroxymethyldihydro
pteridine
pyrophosphokinase

Coenzyme transport and metabolism

18

2.938

0.3

1ex8, 1cbk

3.12

0.15

Cyclin-A2

Essential for the control of the cell cycle at
the G1/S (start) and the G2/M (mitosis)
transitions.

2iw6

2.9327

0.4188

19

Geranyltranstransferas
e

Post-translational modification, protein
turnover, chaperones

1rqi

2.9347

0.4191

20

Scytalone dehydratase

Involved in hydro-lyase activity

6std, 7std,
5std, 4std

3.472

0.295

21

Insulin-like growth
factor 1 receptor

This receptor binds insulin-like growth
factor 1 (IGF1) with a high affinity and
IGF2 with a lower affinity. It has a
tyrosine-protein kinase activity.

2zm3, 3d94

2.971

0.2

22

Dihydrofolate
reductase
/Thymidylate synthase

Nucleotide trans port and metabolism

1tls, 1ju6,
1qzf, 3k2h,
3jsu, 3cl9,
2aaz, 2blc,

3.405

0.63

16

17

158

3cd0, 3cd5,
3ccw, 3cdb


1j3j, 1tvv,
1hvy, 3nrr,
1tlc, 1f28,
1sej, 1tsd,
1o26, 2cfa,

3fnn, 3gwc

23

24

Dihydroorotate
dehydrogenase
homolog,
mitochondrial

-

1tv5, 3i68,
3i65, 1tv5

3.327

0.3714

25

Proto-oncogene
tyrosine-protein kinase
LCK

Tyrosine kinase that plays an essential role
for the selection and maturation of
developing T-cell in the thymus and in
mature T-cell function.

2og8, 3byu,
3byo, 2ofv

3.463

0.3171

26

Mitogen-activated
protein kinase 14

Involved in MAP kinase activity

3e92, 3d83,
3e93, 3fc1,
3huc, 2zb0,

3.136

0.3514

27
159

Angiopoietin-1
receptor

This protein is a protein tyrosine-kinase

transmembrane receptor for angiopoietin 1.
Probably regulates endothelial cell
proliferation, differentiation and guides the
proper pattern

Beta-secretase 1

Involved in aspartic-type signal peptidase

3duy, 2qky,
3f3e, 1ymz,

3.249

0.36

2p4i, 2osc

3.394

0.271


activity

1ym4, 1xs7,
3hvg

Involved in protein kinase activity

1p2a, 1fvt,
1r78, 2vtp,
3bhv

3.55

0.36

29

Tyrosine-protein
phosphatase nonreceptor type 1

May play an important role in CKII- and
p60c-src-induced signal transduction
cascades (By similarity).

1q6s, 1ecv,
1nwe, 1no6,
1c83

3.278

0.293

30

Heat shock protein
HSP 90-alpha

Molecular chaperone. Has ATPase activity
(By similarity).

1uyk, 2wi4,
1uyh, 1uye,
1uyg, 2xdx

3.308

0.399

Phosphatidylinositol
3-kinase regulatory
subunit alpha

Binds to phosphorylated protein-Tyr
kinases, through its SH2 domain, and acts
as an adapter, mediating the association of
the p110 catalytic unit to the plasma
membrane. Necessary for the insulinstimulated increase in glucose uptake.

1pic

2.928

0.3254

28

Cell division protein

kinase 2

31

160


Table XXI Retrieval of top targets of 173c by the ReverseScreen 2D and 3D Methods, PharmMapper and Binding DB
Pharm
Function

PDB ids

(target name)

Mapper

Screen

(fit

3d

score)*

Protein name
S. No.

Reverse

score*

Phosphatidylinositol-4,5bisphosphate-3-kinase

Involved in phosphotransferase activity,
alcohol group as acceptor

2a4z, 2a5u

4.223

0.731

2

Epidermal growth factor
receptor

Cell-surface receptor for members of
the epidermal growth factor family
(EGF-family) of extracellular protein
ligands

2gs7,
1mox, 1ivo

3.915

0.436

3

Phosphoenolpyruvate
carboxykinase, cytosolic
[GTP]

Energy production and conversion

1m51

3.811

0.2683

3.815

0.3462

3.654

0.275

1

4

Involved in protein kinase activity

5

161

Proto-oncogene tyrosineprotein kinase ABL1

1iep, 1fpu,
1hyy, 1opj,
3ms9, 3k5v,
2g2h

Scytalone dehydratase

Involved in hydro-lyase activity

6std, 7std,
5std, 4std


6

7

Pyruvate oxidase

Insulin-like growth factor 1
receptor

1pox, 1pow,
1v5e, 2ez9

3.644

0.233

Binds insulin-like growth factor 1
(IGF1) with a high affinity and IGF2
with a lower affinity. It has a tyrosine2zm3, 3d94
protein kinase activity; necessary for the
activation of the IGF1-stimulated
downstream signaling cascade.

3.6436

0.2

1mrl, 3dho

3.6139

0.2564

4.2659

0.371

3.561

0.375

Amino acid transport and metabolism

8

Streptogramin A
acetyltransferase

Inactivates the A compounds of
streptogramin antibiotics by acetylation,
thus providing resistance to these
antibiotics.

9

Isopentenyl-diphosphate Deltaisomerase

Secondary metabolites biosynthesis,
transport and catabolism

1ppv, 1p0n,
1x84, 1x83,
1vcf, 2zru

Nucleotide transport and metabolism

1tls, 1ju6,
1qzf, 3k2h,
3jsu, 3cl9,
2aaz, 2blc,
1j3j, 1tvv,
1hvy, 3nrr,
1tlc, 1f28,

1sej, 1tsd,
1o26, 2cfa,

10

162

Dihydrofolate reductase
/Thymidylate synthase


3fnn, 3gwc

Mast/stem cell growth factor
receptor

It has a tyrosine-protein kinase activity.
Binding of the ligands leads to the
autophosphorylation of KIT and its
association with substrates such as
phosphatidylinositol 3-kinase (Pi3K)

1t46, 1t46

3.5339

0.25

Angiopoietin-1 receptor

This protein is a protein tyrosine-kinase
transmembrane receptor for
angiopoietin 1. Regulates endothelial
cell proliferation, differentiation and
guides the proper pattern

2p4i, 2osc

3.4989

0.2174

13

Vascular endothelial growth
factor receptor 2

The VEGF-kinase ligand/receptor
signaling system plays a key role in
vascular development and regulation of
vascular permeability.

3dtw, 2p2h

3.4957

0.3095

14

Proto-oncogene
serine/threonine-protein kinase
Pim-1

Involved in protein kinase activity

3bgz, 3bgq

3.471

0.3429

15

Dihydroorotate dehydrogenase
homolog, mitochondrial

-

1tv5, 3i68,
3i65, 1tv5

3.469

0.3714

16

Mitogen-activated protein
kinase 14

Involved in MAP kinase activity

3e92, 3d83,
3e93, 3fc1,

3.441

0.3514

11

12

163


3huc

Beta-secretase 1

Involved in aspartic-type signal
peptidase activity

3duy, 2qky,
3f3e, 1ymz,
1ym4, 1xs7

3.434

0.36

18

Proto-oncogene tyrosineprotein kinase LCK

Tyrosine kinase that plays an essential
role for the selection and maturation of
developing T-cell in the thymus and in
mature T-cell function.

2og8, 3byo,
3byu, 2ofv

3.463

0.3404

19

Tyrosine-protein phosphatase
non-receptor type 1

May play an important role in CKIIand p60c-src-induced signal
transduction cascades (By similarity).

1q6s, 1ecv,
1nwe, 1no6,
1c83

3.565

0.2812

Neprilysin

Biologically important in the
destruction of opioid peptides such as
Met- and Leu-enkephalins by cleavage
of a Gly-Phe bond

1r1i, 1y8j

3.298

0.3548

3.644

0.2258

17

20

21

Amino acid transport and metabolism

22

DNA polymerase I,
thermostable

Replication, recombination and repair

5ktq, .1qss

3.271

0.2326

23

164

Pyruvate oxidase

1pow,
2ez9, 1pox,
1v5e

Renin

Renin is a highly specific
endopeptidase, whose function is to

1bim, 1bil,
2g1o

3.172

0.3784


generate angiotensin I from
angiotensinogen in the plasma, initiating
a cascade of reactions that produce an
elevation of blood pressure and
increased sodium retention by kidney

24

Ribonuclease

Involved in nucleic acid binding

1goy, 1rca,
1rga, 2rok,
1iyb, 1j1f,
3d45, 1rds

3.17

0.3125

3.575

0.3636

25

Involved in protein kinase activity

26

Heat shock protein HSP 90alpha

Molecular chaperone. Has ATPase
activity (By similarity).

1uyk, 2wi4

3.051

0.3939

27

Biotin carboxylase

-

2w71, 2v58

3.025

0.3871

28

Corticosteroid 11-betadehydrogenase isozyme 1

Catalyzes reversibly the conversion of
cortisol to the inactive metabolite
cortisone. Catalyzes reversibly the
conversion of 7-ketocholesterol to 7beta-hydroxycholesterol.

2bel, 3czr,
3ch6

3.453

0.3429

29

165

Cell division protein kinase 2

1p2a, 1fvt,
1r78, 2vtp,
3bhv

Acetyl-CoA carboxylase

Lipid transport and metabolism

1w96,

1od2, 3h0q,

2.993

0.375


2x24
30

Involved in DNA binding

1uk0, 2pqf

2.981

0.3421

31

NADPH-flavin oxidoreductase

Involved in oxidoreductase activity

2bkj, 2h0u,
1bkj

2.977

0.2857

32

Tyrosine-protein kinase JAK2

Plays a role in leptin signaling and
control of body weight. Tyrosine kinase
of the non-receptor type, involved in
interleukin-3 and interleukin-23 signal
transduction.

2b7a, 3kck

2.974

0.2973

33

Trypanothione reductase

Energy production and conversion

1gxf, .1fec,
2wpf, 2jk6

2.973

0.3714

34

Serine/threonine-protein kinase
Chk1

Required for checkpoint mediated cell
cycle arrest in response to DNA
damage. Recognizes the substrate
consensus sequence [R-X-X- S/T].

2e9u, 2c3l,
3jvr

2.972

0.4138

35

Oxygen-insensitive NAD(P)H
nitroreductase

Involved in oxidoreductase activity

1nec, 1kqb,
1icr

2.968

0.35

36

E3 ubiquitin-protein ligase
Mdm2

Involved in zinc ion binding

3lbk, 1ttv

2.967

0.25

37
166

Poly [ADP-ribose] polymerase
1

Major NAD(P)H-flavin

Energy production and conversion

1v5z, 1vfr,

2.972

0.286

oxidoreductase
3-hydroxy-3-methylglutarylcoenzymeA reductase

This transmembrane glycoprotein is the
rate-limiting enzyme of sterol
biosynthesis.

2q1l, 3cd7,
3cd5, 3cda,
1hwk, 3ccz

3.743

0.2773

39

Matrix metalloproteinase-9

May play an essential role in local
proteolysis of the extracellular matrix
and in leukocyte migration. Could play
a role in bone osteoclastic resorption.

1gkc, 2ovx

3.344

0.425

40

Hepatocyte growth factor
receptor

Involved in hepatocyte growth factor
activity

3f82

41

Estradiol 17-betadehydrogenase 1

Lipid transport and metabolism

1i5r

3.1231

0.2632

42

Histone deacetylase 8

Responsible for the deacetylation of
lysine residues on the N-terminal part of
the core histones. Histone deacetylation

gives a tag for epigenetic repression and
plays an important role in
transcriptional regulation, cell cycle
progression.

1t67, 2v5x

3.114

0.3019

43

Peptidyl-prolyl cis-trans
isomerase FKBP1A

May play a role in modulation of
ryanodine receptor isoform-1 (RYR-1),
a component of the calcium release
channel of skeletal muscle sarcoplasmic

1fki, 3odk,

3.067

0.6818

38

167

reticulum.

44

Purine nucleoside
phosphorylase

Nucleotide transport and metabolism

1a9t, 1a9p,
1z36, 1rfg,
3iom, 1k9s,
1odj

45

Proto-oncogene tyrosineprotein kinase Src

-

3g6h, 1o4r,
3f3t, 2h8h

2.998,

0.432

46

Retinoic acid receptor RXRbeta

Nuclear hormone receptor. Involved in
the retinoic acid response pathway.
Binds 9-cis retinoic acid (9C-RA).

1h9u, 2nll

2.973

0.515

Androgen receptor

Steroid hormone receptors are ligandactivated transcription factors that
regulate eukaryotic gene expression and
affect cellular proliferation and
differentiation in target tissues.

3b67, 2pip,
3b68

2.97

0.586

TGF-beta receptor type-1

On ligand binding, forms a receptor

complex consisting of two type II and
two type I transmembrane
serine/threonine kinases. Type II
receptors phosphorylate and activate
type I receptors which
autophosphorylate, binds and activate
SMAD transcriptional

1vjy, 3gxl

2.967

0.4705

47

48

168

3.048

0.68