ABCDEFGHIJKLMNOPQRSTUVWXYZAAABACADAEAFAGAHAIAJAKALAMANAOAPAQARAS
1
IndexTargetOrganismResearcher On Target Reviewer 1 Add your name here!Reviewer 2Reviewer 1 Rating (Good, Bad, OK)Reviewer 2 Rating (Good, Bad, OK)Notes A- Add notes here! Notes BNotes CResearcher(s) on targetStatusOverlap Primer DesignersTail primers DesignerPrefix IDT Ordering (yellow = ordered)Forward Tail Primer in 5' to 3' orientationReverse Tail Primer in 5' to 3' orientationDisease/RelevanceNOTES DType (anhydrase, reductase, phosphatase, etc.)E.C.structure?homolog structure? % coverage on % identitiestransmembrane region?Complex?activity (from Brenda site)assaySOURCE / PIEssentialityDruggabilityTDR Targets Link or EuPath, etcVDS Target pageGene (NOT gene ontology)Amino Acid Sequencesubstrate available?supplierSecond Substrate# of inhibitorsassayknown inhibitorsNotes ENotes FNotes D (a.a. size)
2
1Lactate DehydrogenaseCryptosporidium parvumInaara S.GoodCrystal Structure: http://www.rcsb.org/structure/2FN7
https://www.ncbi.nlm.nih.gov/pubmed/25542170
https://www.sciencedirect.com/science/article/pii/S0020751917301662
CpLDH
Cryptosporidium infection
Dehydrogenase1.1.1.272FN74ND41 predictedno (S)-lactate + NAD+ = pyruvate + NADH + H+
Lactate Dehydrogenase Activity Assay Kitn/aEssential as a regulaor of glycolosis inhibition of this enzyme causes the loss of energy production.
Druggable becayse Gossypol does competitive inhibition with NADH.
TargetSp18 - Lactate dehydogenase (//Cryptosporidium parvum//)..............................................................................................................................................Jacky X.
Tm-LDHA(S)-lactatesigma aldrichNAD+1
https://www.sigmaaldrich.com/content/dam/sigma-aldrich/docs/Sigma/Bulletin/1/mak066bul.pdf
Gossypol321
3
2Lactate DehydrogenaseP. falciparumEduardo C. Good
Lactate dehydrogenase is present in this. PDB structure is available as well (http://www.rcsb.org/structure/2X8L). Causes malaria (very serious)
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3122489/
https://www.cdc.gov/malaria/about/biology/parasites.html
Eduardo C.Eduardo C.PfLDH
TACTTCCAATCCATGATGGCGCCGAAAGCG
GTC ATT TCC ACC TAT TTA CGC GAG TGC TTT CAT ACG TTT GG
MalariaDehydrogenase1.1.1.272X8L4ND41 predictedNo(S)-lactate + NAD+ = pyruvate + NADH + H+
Lactate Dehydrogenase (LDH) Activity Assay KitChan, Kit-Lam
Essential enzyme that regenerates nicotinamide adenine dinucleotide (NAD+) from NADH. Essential for growth.
0.8
http://tdrtargets.org/targets/view?gene_id=2126
N/APF3D7_1324900
ID: 814112
(S)-lactateSigma-AldrichNAD+1
https://www.sigmaaldrich.com/content/dam/sigma-aldrich/docs/Sigma/Bulletin/1/mak066bul.pdf
Gossypol
4
36-phosphogluconate dehydrogenase, decarboxylating, putativeLeishmania majorneeds oligos (Dr. B)homology modelLm6PGDH
Leishmaniasis is a vector-borne disease that is transmitted by sandflies and caused by obligate intracellular protozoa of the genus Leishmania.
dehydrogenase1.1.1.44no
T. brucei (PDB: 1PGJ) 73% identity, 97 % query
no
6-phospho-D-gluconate + NADP+ = D-ribulose 5-phosphate + CO2 + NADPH + H+
Continuous spectrophotmetric Rate DeterminationSteven, MayurThe enzyme participates in the oxidative branch of the pentose phosphate pathway, whose main purpose is to produce NADPH and pentose for biosynthetic reactions. Highly specific for NADP+. cf. EC 1.1.1.343, phosphogluconate dehydrogenase (NAD+-dependent, decarboxylating).0.8
http://tdrtargets.org/targets/view?gene_id=23670
LmjF35.3340
MSNDLGIIGLGVMGANLALNIAEKGFKVAVFNRTYAKTTSFLKEHESEKFAANLNGYETMKEFAASLKKPRRAFILVQAG
AATDSTIEQLKEVFENGDIIIDTGNANFKDQDKRAAQLESQGLRFLGMGISGGEEGARKGPAFFPGGTPSVWEEVRPIVE
AAAAKAEDGRPCVTFNGKGGAGSCVKMYHNAGEYAVLQIWGEAYSALLAFGFDNDQIADVFESWKADGFLKSYMLDISIA
ACRAREATGNYLSEKVKDRIGSKGTGLWSAQEALEIGVPAPSLNMAVISRQMTMYKGERIANCKAFPNFPRGPSEEATDK
SPNSPEAKKLYHAVSLCIIASYAQMFQCLRELDKVYGFGLNLPATIATFRAGCILQGYLLGPMTKAFEENPNLPNLMDAF
TKEIAAGLDDCRQILAKLTVNTAVSLPVMMASLSYINAMYTETLPYGQLVSLQRDVFGRHGYERTDKDGRESFEWPALQ
6 Phosphogluconate ($86.30)
Sigma Aldrich
Beta-Nicotinamide Adenine Dinucleotide, Oxidized form ($89.80)
tons
Continuous spectrophotmetric Rate Determination
http://www.brenda-enzymes.org/enzyme.php?ecno=1.1.1.44
assay methodology: https://www.sigmaaldrich.com/content/dam/sigma-aldrich/docs/Sigma/Enzyme_Assay/6phosphoglucdehydrog75.pdf
479
5
46-phosphogluconate dehydrogenase, decarboxylating, putativeT. cruzi Pareesa H. homology modelTyler G.Tc6pgdh
TACTTCCAATCCATGGACGTTGGCATCGTTGGTC
TATCCACCTTTACTGTTATTGCAGCTCCGGCCACTG
Chagas Diseasedehydrogenase1.1.1.44NoT. brucei (PDB: 1PGJ)NoDimer6-phosphono-D-gluconate + NADP+=D-ribulose 5-phosphate + NADPHContinuous Spectrophotometric Rate Determination at 340nmBella, JosueInvolved in the bacterial pentose phosphate pathway0.6
http://tdrtargets.org/targets/view?gene_id=49268
Not Avaliable
Tc00.1047053510663.70 9 (from Gene DB)
6-Phosphogluconic acid trisodium salt (P7877) $86.30
Sigma Aldrich
β-Nicotinamide adenine dinucleotide phosphate sodium salt hydrate (N0505) $89.80
alot
Continuous spectrophotmetric Rate Determination
http://www.brenda-enzymes.org/enzyme.php?ecno=1.1.1.44&Suchword=&organism%5B%5D=Trypanosoma+cruzi
477
6
5D-alanine:D-alanine ligaseStaphylococcus aureusAnthony Z.Enzyme is essential to the formation of bacterial cell walls and can result in resistance to vanomycinhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC1622796/SaDAL
TACTTCCAATCCATGACCAAAGAGAACATCTGCAT
TATCCACCTTTACTGTTAGTCGATCTTATACTTGTTTTTCTGCTTG
Skin infections, food poisoning, hospital-acquired infectionsCan be commensal but can cause life-threatening diseasesLigase6.3.2.42I80N/AN/ABiological unit = dimerATP + 2 D-alanine = ADP + phosphate + D-alanyl-D-alaninecolorimetric assay for high-throughput inhibitor screeningLiu, SRequired for final step in the synthesis of peptidoglycan (bacterial cell walls)Yes, has been a target before and has been subject to evolution of antibiotic resistanceN/Ahttp://www.genedb.org/web-artemis/?src=scaffold105.1_size92539.2.8344-69665.final&base=49455&bases=3182Yes, D-Ala-D-AlaSigma AldrichATPManycolorimetric assay for high-throughput inhibitor screeningphosphinic acid dipeptide analogues, Diazenedicarboxamides345
7
6D-alanine:D-alanine ligaseBacillus anthracisMosesBaDADA
TACTTCCAATCCATGGCGAACGACTACCTGTTCAC
TATCCACCTTTACTGTTAAGCAACTTGTACCGCCGG
Anthrax
Affects most livestock and humans
Ligase6.3.2.4Yes. 3R5XATP + 2 D-alanine = ADP + phosphate + D-alanyl-D-alanineCombined assay (in vitro method)Required for peptidoglycan layer in cell walls of bacterial species
Yes Ddl can be a target
n/a
ddl (ddlB) 10.2210/pdb3R5X/pdb
Yes; D-alanyl-D-alanine
Sigma AldrichATPTonsCombined assay
http://www.brenda-enzymes.org/enzyme.php?ecno=6.3.2.4#NATURAL%20SUBSTRATES
307
8
7D-alanine:D-alanine ligaseYersinia pestisYpDalaLigase6.3.2.4ATP + 2 D-alanine = ADP + phosphate + D-alanyl-D-alanineCombined assay (in vitro method)Required for peptidoglycan layer in cell walls of bacterial species
Yes Ddl can be a target
n/a
Yes; D-alanyl-D-alanine
Sigma AldrichATPTonsCombined assay
http://www.brenda-enzymes.org/enzyme.php?ecno=6.3.2.4#NATURAL%20SUBSTRATES
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
61
62
63
64
65
66
67
68
69
70
71
72
73
74
75
76
77
78
79
80
81
82
83
84
85
86
87
88
89
90
91
92
93
94
95
96
97
98
99
100