Binding Site Information of Target
| Target General Information | Top | ||||
|---|---|---|---|---|---|
| Target ID | T72881 | Target Info | |||
| Target Name | Leukotriene C4 synthase (LTC4S) | ||||
| Synonyms | Leukotriene-C(4)Leukotriene C4 synthase synthase; Leukotriene-C(4) synthase; LTC4 synthase | ||||
| Target Type | Patented-recorded Target | ||||
| Gene Name | LTC4S | ||||
| Biochemical Class | Carbon-sulfur lyase | ||||
| UniProt ID | |||||
| Drug Binding Sites of Target | Top | |||||
|---|---|---|---|---|---|---|
| Ligand Name: Glutathione | Ligand Info | |||||
| Structure Description | Crystal structure analysis of human leukotriene C4 synthase at 1.9 angstrom resolution | PDB:3PCV | ||||
| Method | X-ray diffraction | Resolution | 1.90 Å | Mutation | No | [1] |
| PDB Sequence |
MKDEVALLAA
10 VTLLGVLLQA20 YFSLQVISAR30 RAFRVSPPLT40 TGPPEFERVY50 RAQVNCSEYF 60 PLFLATLWVA70 GIFFHEGAAA80 LCGLVYLFAR90 LRYFQGYARS100 AQLRLAPLYA 110 SARALWLLVA120 LAALGLLAHF130 LPAALRAALL140 GRLRTL
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| Click to View More Binding Site Information of This Target and Ligand Pair | ||||||
| Ligand Name: Palmitoleic acid | Ligand Info | |||||
| Structure Description | Structure of human Leukotriene C4 synthase mutant R31Q in complex with glutathione | PDB:3LEO | ||||
| Method | X-ray diffraction | Resolution | 2.10 Å | Mutation | Yes | [2] |
| PDB Sequence |
HHHHHHKDEV
5 ALLAAVTLLG15 VLLQAYFSLQ25 VISARQAFRV35 SPPLTTGPPE45 FERVYRAQVN 55 CSEYFPLFLA65 TLWVAGIFFH75 EGAAALCGLV85 YLFARLRYFQ95 GYARSAQLRL 105 APLYASARAL115 WLLVALAALG125 LLAHFLPAAL135 RAALLGRLRT145 |
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| Click to View More Binding Site Information of This Target and Ligand Pair | ||||||
| Ligand Name: Dodecyl-Alpha-D-Maltoside | Ligand Info | |||||
| Structure Description | Crystal structure of Human Leukotriene C4 Synthase in complex with substrate glutathione | PDB:2UUH | ||||
| Method | X-ray diffraction | Resolution | 2.15 Å | Mutation | No | [3] |
| PDB Sequence |
HHHHHHKDEV
5 ALLAAVTLLG15 VLLQAYFSLQ25 VISARRAFRV35 SPPLTTGPPE45 FERVYRAQVN 55 CSEYFPLFLA65 TLWVAGIFFH75 EGAAALCGLV85 YLFARLRYFQ95 GYARSAQLRL 105 APLYASARAL115 WLLVALAALG125 LLAHFLPAAL135 RAALLGRLRT145 L |
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Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .LMU or .LMU2 or .LMU3 or :3LMU;style chemicals stick;color identity;select .A:59 or .A:101 or .A:102 or .A:104 or .A:105 or .A:108 or .A:109 or .A:112 or .A:115 or .A:116 or .A:119; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| Ligand Name: S-hexylglutathione | Ligand Info | |||||
| Structure Description | Human LTC4 synthase in complex with product analogs - implications for enzyme catalysis | PDB:4JRZ | ||||
| Method | X-ray diffraction | Resolution | 2.40 Å | Mutation | No | [4] |
| PDB Sequence |
MHHHHHHKDE
4 VALLAAVTLL14 GVLLQAYFSL24 QVISARRAFR34 VSPPLTTGPP44 EFERVYRAQV 54 NCSEYFPLFL64 ATLWVAGIFF74 HEGAAALCGL84 VYLFARLRYF94 QGYARSAQLR 104 LAPLYASARA114 LFLLVALAAL124 GLLAHFLPAA134 LRAALLGRLR144 TLLPWA |
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Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .GTX or .GTX2 or .GTX3 or :3GTX;style chemicals stick;color identity;select .A:51 or .A:55 or .A:58 or .A:59 or .A:93 or .A:97 or .A:104 or .A:108 or .A:112 or .A:115 or .A:116; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| Click to View More Binding Site Information of This Target and Ligand Pair | ||||||
| Ligand Name: (2R)-2-amino-5-[[(2R)-1-(carboxymethylideneamino)-3-[(2R)-2-hydroxy-4-phenylbutyl]sulfanyl-1-oxopropan-2-yl]amino]-5-oxopentanoic acid | Ligand Info | |||||
| Structure Description | Human LTC4 synthase in complex with product analogs - implications for enzyme catalysis | PDB:4J7Y | ||||
| Method | X-ray diffraction | Resolution | 2.90 Å | Mutation | No | [4] |
| PDB Sequence |
HHHKDEVALL
8 AAVTLLGVLL18 QAYFSLQVIS28 ARRAFRVSPP38 LTTGPPEFER48 VYRAQVNCSE 58 YFPLFLATLW68 VAGIFFHEGA78 AALCGLVYLF88 ARLRYFQGYA98 RSAQLRLAPL 108 YASARALWLL118 VALAALGLLA128 HFLPAALRAA138 LLGRLRTA
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Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .1JP or .1JP2 or .1JP3 or :31JP;style chemicals stick;color identity;select .A:55 or .A:58 or .A:59 or .A:62 or .A:90 or .A:93 or .A:104 or .A:108 or .A:112 or .A:115 or .A:116 or .A:119; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| Ligand Name: Glutathionesulfonic acid | Ligand Info | |||||
| Structure Description | Structure of human Leukotriene C4 synthase in complex with glutathione sulfonate | PDB:3HKK | ||||
| Method | X-ray diffraction | Resolution | 2.90 Å | Mutation | No | [5] |
| PDB Sequence |
HKDEVALLAA
10 VTLLGVLLQA20 YFSLQVISAR30 RAFRVSPPLT40 TGPPEFERVY50 RAQVNCSEYF 60 PLFLATLWVA70 GIFFHEGAAA80 LCGLVYLFAR90 LRYFQGYARS100 AQLRLAPLYA 110 SARALWLLVA120 LAALGLLAHF130 LPAALRAALL140 GRLRT
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Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .GTS or .GTS2 or .GTS3 or :3GTS;style chemicals stick;color identity;select .A:51 or .A:55 or .A:58 or .A:59 or .A:93 or .A:97 or .A:104 or .A:105 or .A:108; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| Ligand Name: D-Gamma-Glutamyl-S-(4-Phenylbutyl)-L-Cysteinylglycine | Ligand Info | |||||
| Structure Description | Human LTC4 synthase in complex with product analogs - implications for enzyme catalysis | PDB:4J7T | ||||
| Method | X-ray diffraction | Resolution | 3.20 Å | Mutation | No | [4] |
| PDB Sequence |
HHHKDEVALL
8 AAVTLLGVLL18 QAYFSLQVIS28 ARRAFRVSPP38 LTTGPPEFER48 VYRAQVNCSE 58 YFPLFLATLW68 VAGIFFHEGA78 AALCGLVYLF88 ARLRYFQGYA98 RSAQLRLAPL 108 YASARALWLL118 VALAALGLLA128 HFLPAALRAA138 LLGRLRTL
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Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .1JO or .1JO2 or .1JO3 or :31JO;style chemicals stick;color identity;select .A:51 or .A:55 or .A:58 or .A:59 or .A:62 or .A:90 or .A:93 or .A:97 or .A:104 or .A:108 or .A:112 or .A:115 or .A:116 or .A:119; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| Ligand Name: Dodecyl 4-O-Alpha-D-Glucopyranosyl-1-Seleno-Beta-D-Glucopyranoside | Ligand Info | |||||
| Structure Description | Human leukotriene C4 synthase in complex with dodecyl-beta-D-selenomaltoside | PDB:3B29 | ||||
| Method | X-ray diffraction | Resolution | 3.20 Å | Mutation | No | [6] |
| PDB Sequence |
KDEVALLAAV
11 TLLGVLLQAY21 FSLQVISARR31 AFRVSPPLTT41 GPPEFERVYR51 AQVNCSEYFP 61 LFLATLWVAG71 IFFHEGAAAL81 CGLVYLFARL91 RYFQGYARSA101 QLRLAPLYAS 111 ARALWLLVAL121 AALGLLAHFL131 PAALRAALLG141 RL
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Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .LSM or .LSM2 or .LSM3 or :3LSM;style chemicals stick;color identity;select .A:7 or .A:10 or .A:11 or .A:12 or .A:13 or .A:14 or .A:59 or .A:64 or .A:68 or .A:73 or .A:74 or .A:75 or .A:77 or .A:78 or .A:80 or .A:81 or .A:84 or .A:104 or .A:105 or .A:108 or .A:109 or .A:112 or .A:115 or .A:116 or .A:119 or .A:124 or .A:125 or .A:127 or .A:128 or .A:131; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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LEU7
3.780
ALA10
4.108
VAL11
4.145
THR12
4.947
LEU13
4.723
LEU14
4.188
TYR59
3.870
LEU64
4.830
TRP68
3.514
PHE73
3.322
PHE74
3.845
HIS75
4.335
GLY77
3.535
ALA78
4.746
ALA80
4.167
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| Ligand Name: (1~{S},2~{S})-2-[5-[cyclopropylmethyl(naphthalen-1-yl)amino]-4-methoxy-pyrimidin-2-yl]carbonylcyclopropane-1-carboxylic acid | Ligand Info | |||||
| Structure Description | Crystal structure of LTC4S in complex with AZ13690257 | PDB:6R7D | ||||
| Method | X-ray diffraction | Resolution | 2.35 Å | Mutation | No | [7] |
| PDB Sequence |
HHHHHHKDEV
5 ALLAAVTLLG15 VLLQAYFSLQ25 VISARRAFRV35 SPPLTTGPPE45 FERVYRAQVN 55 CSEYFPLFLA65 TLWVAGIFFH75 EGAAALCGLV85 YLFARLRYFQ95 GYARSAQLRL 105 APLYASARAL115 WLLVALAALG125 LLAHFLPAAL135 RAALLGRLR
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Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .JUQ or .JUQ2 or .JUQ3 or :3JUQ;style chemicals stick;color identity;select .A:55 or .A:59 or .A:62 or .A:86 or .A:90 or .A:93 or .A:97 or .A:104 or .A:108 or .A:111 or .A:112 or .A:115 or .A:116 or .A:119; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| References | Top | ||||
|---|---|---|---|---|---|
| REF 1 | The catalytic architecture of leukotriene C4 synthase with two arginine residues. J Biol Chem. 2011 May 6;286(18):16392-401. | ||||
| REF 2 | Arginine 104 is a key catalytic residue in leukotriene C4 synthase. J Biol Chem. 2010 Dec 24;285(52):40771-6. | ||||
| REF 3 | Structural basis for synthesis of inflammatory mediators by human leukotriene C4 synthase. Nature. 2007 Aug 2;448(7153):613-6. | ||||
| REF 4 | Crystal structures of leukotriene C4 synthase in complex with product analogs: implications for the enzyme mechanism. J Biol Chem. 2014 Feb 21;289(8):5199-207. | ||||
| REF 5 | Pre-steady state kinetics of human Leukotriene C4 synthase | ||||
| REF 6 | Seleno-detergent MAD phasing of leukotriene C4 synthase in complex with dodecyl--D-selenomaltoside. Acta Crystallogr Sect F Struct Biol Cryst Commun. 2011 Dec 1;67(Pt 12):1666-73. | ||||
| REF 7 | Discovery of the Oral Leukotriene C4 Synthase Inhibitor (1S,2S)-2-({5-[(5-Chloro-2,4-difluorophenyl)(2-fluoro-2-methylpropyl)amino]-3-methoxypyrazin-2-yl}carbonyl)cyclopropanecarboxylic Acid (AZD9898) as a New Treatment for Asthma. J Med Chem. 2019 Sep 12;62(17):7769-7787. | ||||
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