Sandbox Reserved 689 - Revision history

Student: /* Energy Transduction */

Student — Fri, 03 May 2013 03:48:36 GMT

Energy Transduction

←Older revision		Revision as of 03:48, 3 May 2013
Line 32:		Line 32:
	== Energy Transduction ==		== Energy Transduction ==

-	There are <scene name='Sandbox_Reserved_689/Proton_translocation_residues/1'>Four Titrateable Residues</scene> (Asp408, Asp407, Lys940, and Arg 971) whose protonation and deprotonation are suggested to play a large role in the conformational change between the L, T, and O states (Eicher, et al. 2009). ~~PDB: 3D9B~~	+	There are <scene name='Sandbox_Reserved_689/Proton_translocation_residues/1'>Four Titrateable Residues</scene> (Asp408, Asp407, Lys940, and Arg 971) whose protonation and deprotonation are suggested to play a large role in the conformational change between the L, T, and O states (Eicher, et al. 2009). This mechanism has been likened to the proton translocation-driven functional rotation of the monomers in ATP synthase (Pos, 2009).
-		+

	== References ==		== References ==

Student at 03:47, 3 May 2013

Student — Fri, 03 May 2013 03:47:05 GMT

←Older revision		Revision as of 03:47, 3 May 2013
Line 21:		Line 21:
	Because of the large binding pockets in AcrB, it is able to bind and export a wide variety of structurally dissimilar antibiotic drugs such as ethidium, ciprofloxacin, rifampicin, erythromycin, oxacillin, minocycline, acridine, and rhodamine 6G (Pos 2009). The reason for this wide range of substrates is the presence of multiple different entry and binding sites within the AcrB porter domain. Different drugs will bind to different residues in the binding sites depending on their size and polarity. Recent experiments (Nakashima, et al. 2011; Eicher, et al. 2012) have found two main binding sites separated by a		Because of the large binding pockets in AcrB, it is able to bind and export a wide variety of structurally dissimilar antibiotic drugs such as ethidium, ciprofloxacin, rifampicin, erythromycin, oxacillin, minocycline, acridine, and rhodamine 6G (Pos 2009). The reason for this wide range of substrates is the presence of multiple different entry and binding sites within the AcrB porter domain. Different drugs will bind to different residues in the binding sites depending on their size and polarity. Recent experiments (Nakashima, et al. 2011; Eicher, et al. 2012) have found two main binding sites separated by a
	<scene name='Sandbox_Reserved_689/Trigger_loop/3'>switch loop</scene>, which contains three Phe residues (pink). The position of this loop changes in the transition from L to T: in the L conformer, the switch loop occludes some larger drugs from the distal binding pocket. In the T conformer, the switch loop blocks the exit of the drug back into the periplasm.		<scene name='Sandbox_Reserved_689/Trigger_loop/3'>switch loop</scene>, which contains three Phe residues (pink). The position of this loop changes in the transition from L to T: in the L conformer, the switch loop occludes some larger drugs from the distal binding pocket. In the T conformer, the switch loop blocks the exit of the drug back into the periplasm.
		+

	'''Minocycline''' is a lower molecular weight drug (~400 g/mol) and was one of the first to be cocrystallized with AcrB. It binds in the <scene name='Sandbox_Reserved_689/Minocycline_acrb_binding/6'>distal binding pocket</scene> in the T monomer (residues within 4 Angstroms of the drug shown in pink). It is unclear whether the drug skips the proximal binding pocket entirely and goes straight to the distal pocket while the monomer is in the L state, or goes from proximal to distal with the L--T conformation. Here, the <scene name='Sandbox_Reserved_689/Minocycline_acrb_binding_sl/2'>switch loop</scene> can be seen (in green) in front of minocycline, trapping it in the distal binding pocket. <scene name='Sandbox_Reserved_689/Minocycline_acrb_binding/3'>Polar and Nonpolar Interactions</scene> (blue=polar, green=aliphatic, orange=hydrophobic) also hold the drug in the binding pocket.		'''Minocycline''' is a lower molecular weight drug (~400 g/mol) and was one of the first to be cocrystallized with AcrB. It binds in the <scene name='Sandbox_Reserved_689/Minocycline_acrb_binding/6'>distal binding pocket</scene> in the T monomer (residues within 4 Angstroms of the drug shown in pink). It is unclear whether the drug skips the proximal binding pocket entirely and goes straight to the distal pocket while the monomer is in the L state, or goes from proximal to distal with the L--T conformation. Here, the <scene name='Sandbox_Reserved_689/Minocycline_acrb_binding_sl/2'>switch loop</scene> can be seen (in green) in front of minocycline, trapping it in the distal binding pocket. <scene name='Sandbox_Reserved_689/Minocycline_acrb_binding/3'>Polar and Nonpolar Interactions</scene> (blue=polar, green=aliphatic, orange=hydrophobic) also hold the drug in the binding pocket.
Line 35:		Line 36:

	== References ==		== References ==
		+
		+	Eicher, Thomas, et al. 2012. Transport of drugs by the multidrug transporter AcrB involves an access and a deep binding pocket that are separated by a switch-loop. Proceedings of the National Academy of Sciences 109: 5687-5692.
		+
		+	Nakashima, Ryosuke, Keisuke Sakurai, Seiji Yamasaki, Kunihiko Nishino, and Akihito Yamaguchi. 2011. Structures of the multidrug exporter AcrB reveal a proximal multisite drug-binding pocket. Nature 480: 565-570.
		+
		+	Pos, Klaas M. 2009. Drug transport mechanism of the AcrB efflux pump. Biochimica et Biophysica Acta 1794: 782-793.

Student at 03:45, 3 May 2013

Student — Fri, 03 May 2013 03:45:09 GMT

←Older revision		Revision as of 03:45, 3 May 2013
Line 25:		Line 25:


-	'''Rifampicin''' is a high molecular weight drug (~800 g/mol) that has been crystallized in the <scene name='Sandbox_Reserved_689/Rifampicin_in_acrb_monomer/1'>proximal binding pocket</scene> (interacting residues highlighted in teal and shown in ball-and-stick representation). The proximal pocket was only discovered upon cocrystallization of AcrB with large drugs, such as rifampicin and erythromycin. In this case, the switch loop is located <scene name='Sandbox_Reserved_689/Rifampicin_in_acrb_sl/1'>behind the drug</scene> (switch loop is shown in orange). <scene name='Sandbox_Reserved_689/Rifampicin_in_acrb_polar_non/2'>Polar and Nonpolar</scene> interacting residues are shown here (Polar in blue, nonpolar in orange).	+	'''Rifampicin''' is a high molecular weight drug (~800 g/mol) that has been crystallized in the <scene name='Sandbox_Reserved_689/Rifampicin_in_acrb_monomer/1'>proximal binding pocket</scene> (interacting residues highlighted in teal and shown in ball-and-stick representation). The proximal pocket was only discovered upon cocrystallization of AcrB with large drugs, such as rifampicin and erythromycin. In this case, the switch loop is located <scene name='Sandbox_Reserved_689/Rifampicin_in_acrb_sl/2'>behind the drug</scene> (switch loop is shown in orange). <scene name='Sandbox_Reserved_689/Rifampicin_in_acrb_polar_non/2'>Polar and Nonpolar</scene> interacting residues are shown here (Polar in blue, nonpolar in orange).

	(Rifampicin crystal structure from Nakashima, et al. 2011)		(Rifampicin crystal structure from Nakashima, et al. 2011)

Student at 03:39, 3 May 2013

Student — Fri, 03 May 2013 03:39:28 GMT

←Older revision		Revision as of 03:39, 3 May 2013
Line 25:		Line 25:


-	'''Rifampicin''' is a high molecular weight drug (~800 g/mol) that has been crystallized in the <scene name='Sandbox_Reserved_689/~~Rifampicin_in_acrb~~/1'>proximal binding pocket</scene>.	+	'''Rifampicin''' is a high molecular weight drug (~800 g/mol) that has been crystallized in the <scene name='Sandbox_Reserved_689/Rifampicin_in_acrb_monomer/1'>proximal binding pocket</scene> (interacting residues highlighted in teal and shown in ball-and-stick representation). The proximal pocket was only discovered upon cocrystallization of AcrB with large drugs, such as rifampicin and erythromycin. In this case, the switch loop is located <scene name='Sandbox_Reserved_689/Rifampicin_in_acrb_sl/1'>behind the drug</scene> (switch loop is shown in orange). <scene name='Sandbox_Reserved_689/Rifampicin_in_acrb_polar_non/2'>Polar and Nonpolar</scene> interacting residues are shown here (Polar in blue, nonpolar in orange).
-		+
-	<scene name='Sandbox_Reserved_689/~~Rifampicin_in_acrb_monomer~~/1'>~~Binding Pocket Close Up~~</scene>~~, interacting residues~~ (~~all residues within 4 Angstroms) highlighted and~~ shown in ~~ball-and-stick representation~~.	+
-		+
-	<scene name='Sandbox_Reserved_689/Rifampicin_in_acrb_polar_non/2'>Polar and Nonpolar</scene> interacting residues are shown here (Polar in blue, nonpolar ~~in orange).~~	+
-		+
-	~~<scene name='Sandbox_Reserved_689/Rifampicin_in_acrb_sl/1'>in front of switch loop</scene> (switch loop is shown~~ in orange).	+

	(Rifampicin crystal structure from Nakashima, et al. 2011)		(Rifampicin crystal structure from Nakashima, et al. 2011)
Line 38:		Line 32:

	There are <scene name='Sandbox_Reserved_689/Proton_translocation_residues/1'>Four Titrateable Residues</scene> (Asp408, Asp407, Lys940, and Arg 971) whose protonation and deprotonation are suggested to play a large role in the conformational change between the L, T, and O states (Eicher, et al. 2009). PDB: 3D9B		There are <scene name='Sandbox_Reserved_689/Proton_translocation_residues/1'>Four Titrateable Residues</scene> (Asp408, Asp407, Lys940, and Arg 971) whose protonation and deprotonation are suggested to play a large role in the conformational change between the L, T, and O states (Eicher, et al. 2009). PDB: 3D9B
		+
		+
		+	== References ==

Student: /* Substrates */

Student — Fri, 03 May 2013 03:30:51 GMT

Substrates

←Older revision		Revision as of 03:30, 3 May 2013
Line 22:		Line 22:
	<scene name='Sandbox_Reserved_689/Trigger_loop/3'>switch loop</scene>, which contains three Phe residues (pink). The position of this loop changes in the transition from L to T: in the L conformer, the switch loop occludes some larger drugs from the distal binding pocket. In the T conformer, the switch loop blocks the exit of the drug back into the periplasm.		<scene name='Sandbox_Reserved_689/Trigger_loop/3'>switch loop</scene>, which contains three Phe residues (pink). The position of this loop changes in the transition from L to T: in the L conformer, the switch loop occludes some larger drugs from the distal binding pocket. In the T conformer, the switch loop blocks the exit of the drug back into the periplasm.

-	'''Minocycline''' is a lower molecular weight drug (~400 g/mol) and was one of the first to be cocrystallized with AcrB. It binds in the <scene name='Sandbox_Reserved_689/Minocycline_acrb_binding/6'>distal binding pocket</scene> in the T monomer (residues within 4 Angstroms of the drug shown in pink). It is unclear whether the drug skips the proximal binding pocket entirely and goes straight to the distal pocket while the monomer is in the L state, or goes from proximal to distal with the L--T conformation. Here, the <scene name='Sandbox_Reserved_689/Minocycline_acrb_binding_sl/1'>switch loop</scene> can be seen (in green) in front of minocycline, trapping it in the distal binding pocket. <scene name='Sandbox_Reserved_689/Minocycline_acrb_binding/3'>Polar and Nonpolar Interactions</scene> (blue=polar, green=aliphatic, orange=hydrophobic) hold the drug in the binding pocket.	+	'''Minocycline''' is a lower molecular weight drug (~400 g/mol) and was one of the first to be cocrystallized with AcrB. It binds in the <scene name='Sandbox_Reserved_689/Minocycline_acrb_binding/6'>distal binding pocket</scene> in the T monomer (residues within 4 Angstroms of the drug shown in pink). It is unclear whether the drug skips the proximal binding pocket entirely and goes straight to the distal pocket while the monomer is in the L state, or goes from proximal to distal with the L--T conformation. Here, the <scene name='Sandbox_Reserved_689/Minocycline_acrb_binding_sl/2'>switch loop</scene> can be seen (in green) in front of minocycline, trapping it in the distal binding pocket. <scene name='Sandbox_Reserved_689/Minocycline_acrb_binding/3'>Polar and Nonpolar Interactions</scene> (blue=polar, green=aliphatic, orange=hydrophobic) also hold the drug in the binding pocket.

Student: /* Substrates */

Student — Fri, 03 May 2013 03:28:28 GMT

Substrates

←Older revision		Revision as of 03:28, 3 May 2013
Line 22:		Line 22:
	<scene name='Sandbox_Reserved_689/Trigger_loop/3'>switch loop</scene>, which contains three Phe residues (pink). The position of this loop changes in the transition from L to T: in the L conformer, the switch loop occludes some larger drugs from the distal binding pocket. In the T conformer, the switch loop blocks the exit of the drug back into the periplasm.		<scene name='Sandbox_Reserved_689/Trigger_loop/3'>switch loop</scene>, which contains three Phe residues (pink). The position of this loop changes in the transition from L to T: in the L conformer, the switch loop occludes some larger drugs from the distal binding pocket. In the T conformer, the switch loop blocks the exit of the drug back into the periplasm.

-	'''Minocycline''' is a lower molecular weight drug (~400 g/mol) and was one of the first to be cocrystallized with AcrB. It binds in the <scene name='Sandbox_Reserved_689/Minocycline_acrb_binding/6'>distal binding pocket</scene> in the T monomer (residues within 4 Angstroms of the drug shown in pink). It is unclear whether the drug skips the proximal binding pocket entirely and goes straight to the distal pocket while the monomer is in the L state, or ~~whether this drug~~ goes from proximal to distal with the L--T conformation. Here, the <scene name='Sandbox_Reserved_689/Minocycline_acrb_binding_sl/1'>switch loop</scene> ~~is shown~~ (in green) ~~relative to~~ minocycline, ~~which has bypassed~~ the ~~switch loop~~.	+	'''Minocycline''' is a lower molecular weight drug (~400 g/mol) and was one of the first to be cocrystallized with AcrB. It binds in the <scene name='Sandbox_Reserved_689/Minocycline_acrb_binding/6'>distal binding pocket</scene> in the T monomer (residues within 4 Angstroms of the drug shown in pink). It is unclear whether the drug skips the proximal binding pocket entirely and goes straight to the distal pocket while the monomer is in the L state, or goes from proximal to distal with the L--T conformation. Here, the <scene name='Sandbox_Reserved_689/Minocycline_acrb_binding_sl/1'>switch loop</scene> can be seen (in green) in front of minocycline, trapping it in the distal binding pocket. <scene name='Sandbox_Reserved_689/Minocycline_acrb_binding/3'>Polar and Nonpolar Interactions</scene> (blue=polar, green=aliphatic, orange=hydrophobic) hold the drug in the binding pocket.
-		+
-	<scene name='Sandbox_Reserved_689/Minocycline_acrb_binding/3'>Polar and Nonpolar</scene> (blue=polar, green=aliphatic, orange=hydrophobic).	+

Student: /* Substrates */

Student — Thu, 02 May 2013 14:35:42 GMT

Substrates

←Older revision		Revision as of 14:35, 2 May 2013
Line 22:		Line 22:
	<scene name='Sandbox_Reserved_689/Trigger_loop/3'>switch loop</scene>, which contains three Phe residues (pink). The position of this loop changes in the transition from L to T: in the L conformer, the switch loop occludes some larger drugs from the distal binding pocket. In the T conformer, the switch loop blocks the exit of the drug back into the periplasm.		<scene name='Sandbox_Reserved_689/Trigger_loop/3'>switch loop</scene>, which contains three Phe residues (pink). The position of this loop changes in the transition from L to T: in the L conformer, the switch loop occludes some larger drugs from the distal binding pocket. In the T conformer, the switch loop blocks the exit of the drug back into the periplasm.

-	'''Minocycline''' is a lower molecular weight drug (~400 g/mol) and was one of the first to be cocrystallized with AcrB. It binds in the <scene name='Sandbox_Reserved_689/Minocycline_acrb_binding/6'>distal binding pocket</scene> in the T monomer. It is unclear whether the drug skips the proximal binding pocket entirely and goes straight to the distal pocket while the monomer is in the L state, or whether this drug goes from proximal to distal with the L--T conformation. Here, the <scene name='Sandbox_Reserved_689/Minocycline_acrb_binding_sl/1'>switch loop</scene> is shown (in green) relative to minocycline, which has bypassed the switch loop.	+	'''Minocycline''' is a lower molecular weight drug (~400 g/mol) and was one of the first to be cocrystallized with AcrB. It binds in the <scene name='Sandbox_Reserved_689/Minocycline_acrb_binding/6'>distal binding pocket</scene> in the T monomer (residues within 4 Angstroms of the drug shown in pink). It is unclear whether the drug skips the proximal binding pocket entirely and goes straight to the distal pocket while the monomer is in the L state, or whether this drug goes from proximal to distal with the L--T conformation. Here, the <scene name='Sandbox_Reserved_689/Minocycline_acrb_binding_sl/1'>switch loop</scene> is shown (in green) relative to minocycline, which has bypassed the switch loop.

	<scene name='Sandbox_Reserved_689/Minocycline_acrb_binding/3'>Polar and Nonpolar</scene> (blue=polar, green=aliphatic, orange=hydrophobic).		<scene name='Sandbox_Reserved_689/Minocycline_acrb_binding/3'>Polar and Nonpolar</scene> (blue=polar, green=aliphatic, orange=hydrophobic).

Student: /* Substrates */

Student — Thu, 02 May 2013 14:30:42 GMT

Substrates

←Older revision		Revision as of 14:30, 2 May 2013
Line 22:		Line 22:
	<scene name='Sandbox_Reserved_689/Trigger_loop/3'>switch loop</scene>, which contains three Phe residues (pink). The position of this loop changes in the transition from L to T: in the L conformer, the switch loop occludes some larger drugs from the distal binding pocket. In the T conformer, the switch loop blocks the exit of the drug back into the periplasm.		<scene name='Sandbox_Reserved_689/Trigger_loop/3'>switch loop</scene>, which contains three Phe residues (pink). The position of this loop changes in the transition from L to T: in the L conformer, the switch loop occludes some larger drugs from the distal binding pocket. In the T conformer, the switch loop blocks the exit of the drug back into the periplasm.

-	'''~~Rifampicin~~''' is a ~~high~~ molecular weight drug (~~~800~~ g/mol) ~~that has been crystallized~~ in the proximal binding pocket	+	'''Minocycline''' is a lower molecular weight drug (~400 g/mol) and was one of the first to be cocrystallized with AcrB. It binds in the <scene name='Sandbox_Reserved_689/Minocycline_acrb_binding/6'>distal binding pocket</scene> in the T monomer. It is unclear whether the drug skips the proximal binding pocket entirely and goes straight to the distal pocket while the monomer is in the L state, or whether this drug goes from proximal to distal with the L--T conformation. Here, the <scene name='Sandbox_Reserved_689/Minocycline_acrb_binding_sl/1'>switch loop</scene> is shown (in green) relative to minocycline, which has bypassed the switch loop.

-	<scene name='Sandbox_Reserved_689/Rifampicin_in_acrb/1'>~~Bound; entire AcrB trimer shown~~</scene>	+	<scene name='Sandbox_Reserved_689/Minocycline_acrb_binding/3'>Polar and Nonpolar</scene> (blue=polar, green=aliphatic, orange=hydrophobic).
		+
		+
		+	'''Rifampicin''' is a high molecular weight drug (~800 g/mol) that has been crystallized in the <scene name='Sandbox_Reserved_689/Rifampicin_in_acrb/1'>proximal binding pocket</scene>.

	<scene name='Sandbox_Reserved_689/Rifampicin_in_acrb_monomer/1'>Binding Pocket Close Up</scene>, interacting residues (all residues within 4 Angstroms) highlighted and shown in ball-and-stick representation.		<scene name='Sandbox_Reserved_689/Rifampicin_in_acrb_monomer/1'>Binding Pocket Close Up</scene>, interacting residues (all residues within 4 Angstroms) highlighted and shown in ball-and-stick representation.
Line 33:		Line 36:

	(Rifampicin crystal structure from Nakashima, et al. 2011)		(Rifampicin crystal structure from Nakashima, et al. 2011)
-
-	'''Minocycline''' is a lower molecular weight drug (~400 g/mol) that has been crystallized in the <scene name='Sandbox_Reserved_689/Minocycline_acrb_binding/6'>distal binding pocket</scene>.
-
-
-	<scene name='Sandbox_Reserved_689/Minocycline_acrb_binding_sl/1'>behind the switch loop</scene> (switch loop shown in green)
-
-	<scene name='Sandbox_Reserved_689/Minocycline_acrb_binding/3'>Polar and Nonpolar</scene> (blue=polar, green=aliphatic, orange=hydrophobic).

	== Energy Transduction ==		== Energy Transduction ==

	There are <scene name='Sandbox_Reserved_689/Proton_translocation_residues/1'>Four Titrateable Residues</scene> (Asp408, Asp407, Lys940, and Arg 971) whose protonation and deprotonation are suggested to play a large role in the conformational change between the L, T, and O states (Eicher, et al. 2009). PDB: 3D9B		There are <scene name='Sandbox_Reserved_689/Proton_translocation_residues/1'>Four Titrateable Residues</scene> (Asp408, Asp407, Lys940, and Arg 971) whose protonation and deprotonation are suggested to play a large role in the conformational change between the L, T, and O states (Eicher, et al. 2009). PDB: 3D9B

Student: /* Substrates */

Student — Thu, 02 May 2013 14:13:27 GMT

Substrates

←Older revision		Revision as of 14:13, 2 May 2013
Line 19:		Line 19:
	== Substrates ==		== Substrates ==

-	Because of the large binding pockets in AcrB, it is able to bind and export a wide variety of antibiotic drugs and ~~other toxins~~.	+	Because of the large binding pockets in AcrB, it is able to bind and export a wide variety of structurally dissimilar antibiotic drugs such as ethidium, ciprofloxacin, rifampicin, erythromycin, oxacillin, minocycline, acridine, and rhodamine 6G (Pos 2009). The reason for this wide range of substrates is the presence of multiple different entry and binding sites within the AcrB porter domain. Different drugs will bind to different residues in the binding sites depending on their size and polarity. Recent experiments (Nakashima, et al. 2011; Eicher, et al. 2012) have found two main binding sites separated by a
		+	<scene name='Sandbox_Reserved_689/Trigger_loop/3'>switch loop</scene>, which contains three Phe residues (pink). The position of this loop changes in the transition from L to T: in the L conformer, the switch loop occludes some larger drugs from the distal binding pocket. In the T conformer, the switch loop blocks the exit of the drug back into the periplasm.

	'''Rifampicin''' is a high molecular weight drug (~800 g/mol) that has been crystallized in the proximal binding pocket		'''Rifampicin''' is a high molecular weight drug (~800 g/mol) that has been crystallized in the proximal binding pocket

Student: /* Structural Elements */

Student — Thu, 02 May 2013 13:42:10 GMT

Structural Elements

←Older revision		Revision as of 13:42, 2 May 2013
Line 15:		Line 15:
	The AcrB pump is a homotrimer with monomers of 1049 amino acids. The protein has three domains: a transmembrane domain that spans the inner membrane of the bacterium and is responsible for energy transduction, a porter domain which is responsible for selectivity and transport of substrate, and a TolC docking domain that funnels exported substrate into the TolC channel protein. These domains are made up of <scene name='Sandbox_Reserved_689/Secondary_structure/2'>secondary structures</scene>: alpha helices in the TM region and a mixture of alpha helices and beta sheets in the other two domains. There is a lot of "random coil" (shown in blue) inside the porter domain of each monomer. Many of the residues responsible for binding and moving substrate are found in these primary structures.		The AcrB pump is a homotrimer with monomers of 1049 amino acids. The protein has three domains: a transmembrane domain that spans the inner membrane of the bacterium and is responsible for energy transduction, a porter domain which is responsible for selectivity and transport of substrate, and a TolC docking domain that funnels exported substrate into the TolC channel protein. These domains are made up of <scene name='Sandbox_Reserved_689/Secondary_structure/2'>secondary structures</scene>: alpha helices in the TM region and a mixture of alpha helices and beta sheets in the other two domains. There is a lot of "random coil" (shown in blue) inside the porter domain of each monomer. Many of the residues responsible for binding and moving substrate are found in these primary structures.

-	<scene name='Sandbox_Reserved_689/Monomer_rainbow/1'>N~~-->~~C ~~Rainbow~~</scene>	+	A monomer colored red to blue from <scene name='Sandbox_Reserved_689/Monomer_rainbow/1'>N to C terminus</scene> shows that the three domains are not assembled according to the order of their primary structure.
-		+
-		+
-		+
-		+

	== Substrates ==		== Substrates ==