Deep Cholesterol Binding Sites    Anthony Lee - University of Southampton

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Deep Cholesterol Binding Sites

• Introduction
• GPCR Class A
• Rhodopsin and Opsin
• GPCR Class B
• GPCR Class C
• GPCR Class F
• Adiponectin Receptor
• Ion Channels
• Porins Etc.
• Transporters
• Other Membrane Proteins

Interfacial Cholesterol Binding Sites

• GPCR Class A [Part 1]
• GPCR Class A [Part 2]
• GPCR Class B
• GPCR Class C
• GPCR Class F
• Adiponectin Receptor
• TRPA-TRPN channels
• TRPP-TRPV channels

Deep Cholesterol Binding Sites on Mammalian Membrane Proteins

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Other Membrane Proteins

[Letters refer to subunits as given in the PDB file, followed by the TM helix number: Units of E, kcals/mol with molar concentration units]

E	Donor		Acceptor		Local Residues (within 3 Å of a cholesterol –OH group)
Novel Receptors
STRA6 retinol uptake receptor, zebra fish, 5sy1
-7.3	Chl	OH	Ser48 [A1]	OG	Ala45 [A1]	Ser48 [A1]	Leu49 [A1]
-6.4	Chl	OH	Thr133 [A3]	OG1	Leu129 [A3]	Thr133 [A3]
-6.0	Chl	OH	Ala191 [A5]	O	Ala191 [A5]	Cys192 [A5]
Tetraspanins
CD81 tetraspanin, human, 5tcx
None
Intramembrane Proteases
CAAX protease ZMPSTE24, human, 4aw6
-11.5	Chl	OH	Ser208 [5]	OG	Thr204 [5]	Ser208 [5]	Gln353 [6]
-11.5	Chl	OH	Thr204 [5]	OG1	Thr204 [5]	Leu205 [5]	Ser208 [5]	Gln353 [6]
-10.6	Chl	OH	Glu86. [2]	OE2	Glu86 [2]	Thr90 [2]
CAAX protease ZMPSTE24, mutant, complex with tetrapeptide, human, 2ypt
-11.2	Chl	OH	Ser208 [5]	OG	Thr204 [5]	Ser208 [5]	Gln353 [6]
-10.1	Chl	OH	Glu86 [2]	OE2	Glu86 [2]	Thr90 [2]
-8.8	Chl	OH	Ser134 [3]	OG	Ala130 [3]	Thr131 [3]	Ser134 [3]
-8.4	Chl	OH	Ser208 [5]	OG	Thr204 [5]	Leu205 [5]	Ser208 [5]	Gln353 [6]
	Chl	OH	Thr204 [5]	OG1
γ-secretase, human, 5a63 5a63
-7.3	Chl	OH	Thr99 [B1]	OG1	Val95 [B1]	Ala98 [B1]	Thr99 [B1]
-6.4	Chl	OH	Tyr181 [B2]	OH	Thr99 [B1]	Tyr181 [B2]
	Tyr181 [B2]	OH	Chl	OH
Membrane-associated proteins in Eicosanoid and Glutathione metabolism proteins (MAPEG)
Microsomal Glutathione transferase I, rat, 2h8a
-6.3	Chl	OH	Phe134 [B4]	O	Phe133 [B4]	Phe134 [B4]	Tyr137 [B4]	Gly138 [B4]
-6.2	Chl	OH	Tyr115 [C3]	OH	Tyr115 [C3]
	Tyr115 [C3]	OH	Chl	OH
Microsomal prostaglandin E synthase, human, 3dww
-6.7	His102 [A3]	ND1	Chl	OH	Met101 [A3]	His102 [A3]
-6.7	Chl	OH	Gln134 [A4]	O	Gln134 [A4]	Cys137 [A4]	Ala138 [A4]
-6.4	Chl	OH	Leu132 [A4]	O	Val105 [A3]	Gly109 [A3]	Leu132 [A4]
-6.2	Chl	OH	Ser139 [A4]	OG	Leu135 [A4	Pro136 [A4	Ser139 [A4
Microsomal prostaglandin E synthase, human, 4al0
None
5-lipoxygenase-activating protein, human, 2q7m
None
Leukotriene LTC-4 synthase, human, 2pno
None
Leukotriene LTC-4 synthase, human, 2uuh
None
LeukotrieneLTC-4 synthase with bound leukotriene analog I, human, 4jcz
None
LeukotrieneLTC-4 snythase mutant with bound leukotriene analog I, human, 4jrz
None
LeukotrieneLTC-4 synthase with bound leukotriene analog II, human, 4j7t
None
LeukotrieneLTC-4 synthase with bound leukotriene analog III, human, 4j7y
None
Sterol-Sensing Domain (SSD) Proteins
Niemann-Pick C1 protein, human, 5u73
-6.5	Chl	OH	Thr743 [6]	OG1	Thr743 [6]	Val744 [6]
-6.0	Ser666 [4]	OG	Chl	OH	Leu662 [4]	Ile663 [4]	Ser666 [4]
Niemann-Pick C1 protein, human, 5u74
-6.6	Chl	OH	His1239 [13]	ND1	Thr1238 [13]	His1239 [13]
-6.4	Ser666 [4]	OG	Chl	OH	Leu662 [4]	Ser666 [4]
-6.2	Chl	OH	Thr743 [6]	OG1	Phe740 [6]	Thr743 [6]	Val744 [6]
Palmitoyl Transferase
Palmitoyl transferase, human, 6bml
None
Palmitoyl transferase, human, 6bmm
-5.9	Chl	OH	Thr23 [1]	OG1	Thr23 [1]
Palmitoyl transferase, human, 6bmn
-5.5	Chl	OH	Thr23 [1]	OG1	Val19 [1]	Leu20 [1]	Thr23 [1]
Fatty Acid Desaturase
Stearoyl-coenzyme A desaturase (SCD1), with substrate [ih, inner helix, human, 4zyo
-7.7	Chl	OH	Tyr108 [2]	OH	Tyr108 [2]	Leu290 [ ih]	Gly291 [ ih]
-7.2	Chl	OH	Thr231 [3]	OG1	Phe227 [3]	Thr231 [3]	Thr250 [4]
Stearoyl-coenzyme A desaturase (SCD1), with substrate, mouse, 4ymk
-7.2	Chl	OH	Thr106 [2]	OG1	Phe102 [2]	Met105 [2]	Thr106 [2]
Hydrolases
Estrone sulphatase, placenta, human, 1p49
-5.9	Chl	OH	Thr196 [1]	OG1	Ile192 [1]	Thr196 [1]
Electron Transport Chain Complex II
Succinate:ubiquinone oxidoreductase (SQR, Complex II), heart, chicken, 2fbw
-5.7	Chl	OH	Ala90 [C2]	O	Ala90 [C2]	Leu91 [C2]	Pro94 [C2]
	Chl	OH	Leu91 [C2]	O
Succinate:ubiquinone oxidoreductase (SQR, Complex II) with TEO, heart, chicken, 2h88
None
Succinate:ubiquinone oxidoreductase (SQR, Complex II), heart, pig, 1zoy
-8.6	Chl	OH	Thr77 D2]	OG1	Ala74 [D2]	Thr77 [D2]	Leu78 [D2]
Succinate:ubiquinone oxidoreductase (SQR, Complex II),  chicken, 1yq3
-5.7	Chl	OH	Tyr73 D3]	OH	Tyr73 [D3]
	Tyr73 [D3]	OH	Chl	OH
Succinate:ubiquinone oxidoreductase (SQR, Complex II),  worm, 3vr8
-7.2	Chl	OH	Thr132 [C2]	OG1	Ile128 [C2]	Ala129 [C2]	Thr132 [C2]
-6.4	Chl	OH	Thr85 [C1]	OG1	Ala81 [C1]	Thr85 [C1]
	Thr85 [C1]	OG1	Chl	OH
-6.0	Chl	OH	Ile123 [C2]	O	Ile123 [C2]	Ile124 [C2]
	Chl	OH	Ile124 [C2]	O
Electron Transport Chain Complex III Cytochrome bc1)
Cytochrome bc1, bovine heart, 1bgy
-9.6	Chl	OH	Tyr358 [C8]	OH	Ser297 [C6]	Tyr358 [C8]
-8.1	Ser34 [K1]	OG	Chl	OH	Val25 [J1]	Ala28 [J1]	Leu29 [J1]	Ser34 [K1]
-7.8	Chl	OH	Thr334 [C7]	OG1	Ala330 [C7]	Asp331 [C7]	Thr334 [C7]
Cytochrome bc1, bovine heart,[subunits renamed to match 1bgy], 1pp9
-7.5	Chl	OH	Asp331 [C7]	OD1	Ala330 [C7]	Asp331 [C7]	Thr334 [C7]
-7.2	Chl	OH	Tyr358 [C8]	OH	Ser297  [C6]	Tyr358 [C8]
-7.1	Chl	OH	Thr42 [E1]	OG1	Thr42 [E1]
Cytochrome bc1, bovine heart,[subunits renamed to match 1bgy], 5nmi
-8.0	Chl	OH	Ser34 [K1]	OG	Gly31 [K1]	Ser34 [K1]	Ala35 [K1]
	Ser34 [K1]	OG	Chl	OH
Cytochrome bc1, with inhibitor, bovine heart, 2fyu
-8.8	Chl	OH	Tyr358 [C8]	OH	Ser297 [C6]	Tyr358 [C8]
-7.9	Chl	OH	Asp331 [C7]	OD2	Ala330 [C7]	Asp331 [C7]	Thr334 [C7]
Cytochrome bc1,  bovine heart,[subunits renamed to match 1bgy],   1ntm
-8.6	Chl	OH	Tyr358 [C8]	OH	Ser297 [C6]	Ile298 [C6]	Tyr358 [C8]
Cytochrome bc1, bovine heart,[subunits renamed to match 1bgy], 1l0l
-9.0	Chl	OH	Tyr358 [C8]	OH	Ser297 [C6]	Leu301 [C6]	Tyr358  [C8]
-8.0	Chl	OH	Asp331  [C7]	OD1	Ala330  [C7]	Asp331 [C7]	Thr334  [C7]
-8.0	Chl	OH	Thr44 [E1]	OG1	Thr44 [E1]	Ala48 [E1]
Cytochrome bc1, human, [subunits renamed to match 1bgy], 5xte
-8.1	Chl	OH	Ala126 [E1]	O	Ala126 [E1]	Lys130 [E1]
-6.9	Chl	OH	Ser238 [C5]	OG	Leu234 [C5]	Phe235 [C5]	Ser238 [C5]
Electron Transport Chain Complex IV (Cytochrome c Oxidase)
Cytochrome c oxidase, fully oxidised, [early structure], bovine heart, 1occ
-7.2	Chl	OH	Ser27 [G1]	OG	Leu23 [G1]	Ala24 [G1]	Ser27 [G1]
-7.1	Chl	OH	His151 [A4]	ND1	His151 [A4]	Thr207 [A5]
-7.0	Chl	OH	Thr48 [C2]	OG1	Met44 [C2]	Thr48 [C2]
-6.9	Chl	OH	Thr95 [C3]	OG1	Val91 [C3]	Thr95 [C3]
Cytochrome c oxidase,fully oxidised, bovine heart, 1v54
-8.5	Chl	OH	Ser89 [C3]	OG	Ser89 [C3]	Glu90 [C3]
-7.6	Chl	OH	Thr174 [C5]	OG1	Gly170 [C5]	Val171 [C5]	Thr174 [C5]	Ser212 [C6]
-7.3	Chl	OH	Thr48 [C2]	OG1	Met44 [C2]	Thr48 [C2]
-7.2	Chl	OH	Ser28 [I1]	OG	Ala24 [I1]	Ser28 [I1]
Cytochrome c oxidase,fully reduced, bovine heart, 1v55
-8.4	Chl	OH	Ser89 [C3]	OG	Ser89 [C3]
-7.8	Chl	OH	Ser212 [C6]	OG	Gly170 [C5]	Thr174 [C5]	Ser212 [C6]
	Chl	OH	Thr174 [C5]	OG1
-7.4	Chl	OH	Thr48 [C2]	OG1	Met44 [C2]	Leu47 [C2]	Thr48 [C2]
-7.2	Chl	OH	Ser27 [G1]	OG	Leu23 [G1]	Ala24 [G1]	Ser27 [G1]
Cytochrome c oxidase,with bound cyanide, bovine heart, 3x2q
-8.3	Chl	OH	Ser89 [C3]	OG	Ser89 [C3]	Glu90 [C3]
-7.2	Chl	OH	Thr48 [C2]	OG1	Met44 [C2]	Thr48 [C2]
-7.2	Chl	OH	Ser212 [C6]	OG	Gly170 [C5]	Thr174 [C5]	Ser212 [C6]
	Chl	OH	Thr174 [C5]	OG1
-7.0	Chl	OH	Ser28 [I1]	OG	Ala24 [I1]	Ser28 [I1]
-7.0	Chl	OH	Ser27 [G1]	OG	Leu23 [G1]	Ala24 [G1]	Ser27 [G1]
Cytochrome c oxidase,with bound cytochrome c, bovine heart, 5iy5
-8.8	Chl	OH	Ser89 [C3]	OG	Ser89 [C3]
-7.8	Chl	OH	Ser212 [C6]	OG	Gly170 [C5]	Thr174 [C5]	Ser212 [C6]
	Chl	OH	Thr174 [C5]	OG1
-7.2	Chl	OH	Thr48 [C2]	OG1	Met44 [C2]	Leu47 [C2]	Thr48 [C2]
Cytochrome c oxidase,at neutral pH, bovine heart, 5xdq
-8.6	Chl	OH	Ser89 [C3]	OG	Ser89 [C3]
-8.2	Chl	OH	Ser212 [C6]	OG	Gly170 [C5]	Thr174 [C5]	Ser212 [C6]
	Chl	OH	Thr174 [C5]	OG1
-7.6	Chl	OH	Thr48 [C2]	OG1	Met44 [C2]	Thr48 [C2]