. Author manuscript; available in PMC: 2021 Apr 6.

Published in final edited form as: Chem Rev. 2014 Apr 10;114(11):5815–47. doi: 10.1021/cr400401e

Table 4. Classification of all known three-dimensional structures of wild-type and synthetic conopeptides into folds and sub-folds.

Name^a	Species^b	Cys frame work^c	Size (aa)	# Cys^d	Loop size^e	Gene super family	Method^f	BMRB ID^g	PDB ID^g	Cono Server ID^g
Fold A: four cysteines, globular [connectivity 1-3, 2-4]
Sub-fold A1 (one turn of helix in first loop)
α-ImI	C. imperialis	I	12	4	4/3	A	NMR		1G2G, 1IMI, 1CNL, 1IM1	5, 24, 25, 27
							X-ray		2BYP, 2C9T	34, 35
α-ImI [D5N]		I	12	4	4/3		NMR	4847	1E76	10
α-ImI [R7L]		I	12	4	4/3		NMR	4846	1E75	9
α-ImI [A9L,W10Y,R11ABA]		I	12	4	4/3		NMR	20107		131
α-ImI [R11E]		I	12	4	4/3		NMR	4845	1E74	8
α-ImI [C2Agl,C8Agl]		I	12	2	4/3		NMR	20033		128
α-ImI [C2U,C8U]		I	12	4	4/3		NMR	6897	2BC7	97
α-ImI [C2U,C3U,C8U,C12U]		I	12	4	4/3		NMR	6896	2BC8	98
α-RgIA	C. regius	I	12	4	4/3	A	NMR	20002, 15435	2JUT	118, 123
α-RgIA [D5E]		I	12	4	4/3		NMR	15367	2JUR	119
α-RgIA [P6V]		I	12	4	4/3		NMR	15436	2JUQ	121
α-BuIA	C. bullatus	I	13	4	4/4	A	NMR	15031	2I28	7
α-AuIB	C. aulicus	I	15	4	4/6	A	NMR		1MXN, 1DG2	31, 13
cyclic-AuIB-4 (GGAA)		I	19	4	4/6		NMR			142
cyclic-AuIB-5 (AGAGA)		I	20	4	4/6		NMR			143
cyclic-AuIB-6 (GGAAGG)		I	21	4	4/6		NMR			144
α-EI	C. ermineus	I	18	4	4/7	A	NMR		1K64	18
α-Epi [sTy15>Y]		I	16	4	4/7		X-ray		1A0M	20
α-GIC	C. geographus	I	16	4	4/7	A	NMR	5985	1UL2	26
α-GID	C. geographus	I	18	4	4/7	A	NMR	5585	1MTQ	15
α-MII	C. magus	I	16	4	4/7	A	NMR		1M2C, 1MII	21, 29
α-MII [E11A]		I	16	4	4/7		NMR			145
cyclic-MII-6		I	22	4	4/7		NMR	6818	2AJW	32
cyclic-MII-7		I	23	4	4/7		NMR	6817	2AK0	33
α-OmIA	C. omaria	I	17	4	4/7	A	NMR	6237	2GCZ	5
α-PeIA	C. pergrandis	I	16	4	4/7	A	NMR			139
α-PIA	C. purpurascens	I	18	4	4/7	A	NMR	6720	1ZLC	36
α-Pni1		I	16	4	4/7		X-ray		1PEN	12
α-PnIA [A10L,D14K,sTy15Y]		I	16	4	4/7		X-ray		2BR8	30
α-PnIB	C. pennaceus	I	16	4	4/7	A	X-ray		1AKG	16
ρ-TIA	C. tulipa	I	19	4	4/7	A	NMR		1IEN	65
α-TxIA	C. textile	I	16	4	4/7	A	X-ray		2UZ6	110
α-Vc1.1	C. victoriae	I	16	4	4/7		NMR	7177	2H8S	4
cyclic-Vc1.1		I	22	4	4/7		NMR			149
α-Vc1.2	C. victoriae	I	16	4	4/7	A	NMR	20126		141
Sub-fold A2 (no turn of helix in first loop)
α-CnIA	C. consors	I	14	4	3/5		NMR		1B45	53
α-GI	C. geographus	I	13	4	3/5	A	NMR		1XGA	22
							X-ray		1NOT	11
α-GI [N4Benzoy1-phenylalanine]		I	13	4	3/5		NMR		2FRB	3
α-GI [S12Benzoy1-phenylalanine]		I	13	4	3/5		NMR		2FR9	2
α-SI	C. striatus	I	13	4	3/5	A	NMR	4503	1QMW	1
							X-ray		1HJE	17
α-LtXIVA	C. litteratus	XIV	13	4	3/3/2	L	NMR	21014		148
Sub-fold A3 (no turn of helix in first loop, second loop similar to sub-fold A1)
χ-CMrVIA [K6P]		X	11	4	4/2		NMR		2IH6	111
χ-CMrVIA [K6P] amidated		X	11	4	4/2		NMR		2IH7	112
Fold B: six cysteines, three disulfide bonds not in a knotted arrangement [connectivity 1-4, 2-5, 3-6]
Sub-fold B1 (one turn of helix in second loop, two turns of helix overall)
μ-CnIIIC	C. consors	III	22	6	5/4/5		NMR		2YEN	150
μ-GIIIA	C. geographus	III	22	6	5/4/4	M	NMR	1664, 1665	1TCG, 1TCJ	82, 84, 134, 135
μ-GIIIA [R13A]		III	22	6	5/4/4		NMR		1TCH,1TCK	83, 85
μ-GIIIB	C. geographus	III	22	6	5/4/4	M	NMR		1GIB	64
μ-KIIIA	C. kinoshitai	III	16	6	5/4/4	M	NMR	20048		129
μ-PIIIA	C. purpurascens	III	22	6	5/4/4	M	NMR	6027	1R9I	79
μ-RIIIK [T24A]		III	24	6	6/4/4		NMR			146
μ-SIIIA	C. striatus	III	20	6	1/4/5	M	NMR	20025		125
μ-SmIIIA	C. stercusmuscarum	III	22	6	5/4/5	M	NMR	5881,	1Q2J	77
μ-TIIIA	C. tulipa	III	22	6	5/4/4	M	NMR	20024		126
Sub-fold B2 (no turn of helix in second loop, one turn of helix overall)
α-PIIIE	C. purpurascens	III	24	6	4/5/4	M	NMR	5113	1AS5, 1JLO	51, 68
α-PIIIF	C. purpurascens	III	24	6	4/5/4	M	NMR	5112	1JLP	69
Fold C: six cysteines, three disulfide bonds forming a cystine knot [connectivity 1-4, 2-5, 3-6]
Sub-fold C1 (six residues in first loop)
δ-Am2766	C. amadis	VI/VII	26	6	6/6/3/3	O1	NMR		1YZ2	94
ω-CVID	C. catus	VI/VII	27	6	6/6/3/6	O1	NMR			138
δ-EVIA	C. ermineus	VI/VII	32	6	6/9/3/3	O1	NMR		1G1P, 1G1Z	62, 63
ω-FVIA	C. fulmen	VI/VII	25	6	6/6/3/4		NMR		2KM9	137
μ-conotoxin-GS	C. geographus	VI/VII	27	6	6/3/4/7	O1	NMR		1AG7	50
ω-GVIA	C. geographus	VI/VII	27	6	6/6/2/6	O1	NMR		2CCO, 1TTL, 1OMC	72, 89, 100
ω-GVIA [O10>K]		VI/VII	27	6	6/6/2/6		NMR		1TR6	86
μ-MrVIB	C. marmoreus	VI/VII	31	6	6/9/4/4	O1	NMR	6135	1RMK	80
ω-MVIIA	C. magus	VI/VII	25	6	6/6/3/4	O1	NMR		1DW4, 1DW5, 1MVI, 1OMG, 1TTK	55, 56, 70, 73, 88
ω-MVIIA with C-terminal Gly		VI/VII	26	6	6/6/3/4		NMR		1FEO	59
ω-MVIIA [R10>K]		VI/VII	25	6	6/6/3/4		NMR		1TT3	87
ω-MVIIC	C. magus	VI/VII	26	6	6/6/3/5		NMR	4500	1CNN, 1OMN	74
ω-MVIIC [S17K,S19R,K25R]		VI/VII	26	6	6/6/3/5		NMR		1V4Q	90
κ-PVIIA	C. purpurascens	VI/VII	27	6	6/6/3/5	O1	NMR		1AV3, 1KCP	46
ω-SO3	C. striatus	VI/VII	25	6	6/6/3/4	O1	NMR		1FYG	61
ω-SVIB	C. striatus	VI/VII	26	6	6/6/3/5	O1	NMR		1MVJ	71
t7a	C. tulipa	VI/VII	30	6	6/3/4/4	O1	NMR		1EYO	57
ω-TxVII	C. textile	VI/VII	26	6	6/6/3/3	O1	NMR		1F3K	58
δ-TxVIA	C. textile	VI/VII	27	6	6/6/3/4	O1	NMR		1FU3	60
ι-RXIA	C. radiatus	XI	46	8	6/5/2/4	I1	NMR	15175	2P4L, 2JTU	104, 130
ι-RXIA [BTr33>W]		XI	46	8	6/5/2/4		NMR	15174	2JRY	105
Sub-fold C2 (three residues in first loop)
gm9a	C. gloriamaris	IX	27	6	3/5/3/1/4	P	NMR		1IXT	67
Fold D: four cysteines, disulfide bonds with ribbon connectivity [connectivity 1-4, 2-3]
Sub-fold D1 (disulfide 2-3 in a staple conformation)
χ-MrIA	C. marmoreus	X	13	4	4/2	T	NMR	6891	2EW4	102
cyclic-MrIA		X	15	4	4/2		NMR		2J15	49
χ-MrIB amidated	C. marmoreus	X	13	4	4/2		NMR		1IEO	66
*α-GI ribbon isoform		I	13	4	3/5		NMR		1XGB	23
Sub-fold D2 (disulfide 2-3 in a hook conformation)
*α-AuIB ribbon isoform		I	15	4	4/6		NMR		1MXP	14
*α-BuIA ribbon isoform		I		4	4/4		NMR		2NS3	114
*α-ImI deamidated ribbon isoform		I	12	4	4/3		NMR		2IGU	106
*α-ImI [P6A] ribbon isoform		I	12	4	4/3		NMR		2IFI	108
*α-ImI [P6K] ribbon isoform		I	12	4	4/3		NMR		2IFZ	107
*α-ImI [P6K] ribbon deamidated isoform		I	12	4	4/3		NMR		2IFJ	109
*χ-CMrVIA ribbon isoform			11	4	4/2				2B5P	95
*χ-CMrVIA amidated ribbon isoform		X	11	4	4/2		NMR		2IHA	113
Fold E: four cysteines, mirror of fold A [connectivity 1-3, 2-4]
χ-CMrVIA	C. marmoreus	X	11	4	4/2		NMR		2B5Q	96
Fold F: four cysteines, disulfide bonds collinear [connectivity 1-3, 2-4]
α-Pu14a	C. pulicarius	XIV	23	4	10/1/3	A	NMR	21015		147
Fold G: four cysteines, parallel disulfide bonds [connectivity 1-3, 2-4]
κ-PlXIVA	C. litteratus	XIV	25	4	3/10/1	J	NMR	6951	2FQC	103
Kunitz fold: large protein with two disulfide bonds [connectivity 1-4,2-3]
Conkunitzin-S1	C. striatus	XIV	60	4	24/20/3		X-ray		1Y62	48
Conkunitzin-S2	C. striatus	XIV	65	4	24/20/3		NMR		2j6d	117
Fold H: six cysteines [connectivity 1-5, 2-4, 3-6]
mr3e	C. marmoreus	III	16	6	4/3/1	M	NMR	15195	2EFZ	101
Fold I: six cysteines [connectivity 1-5, 2-3, 4-6]
α-PIVA [Hyp7P,Hyp13P]		IV	25	6	7/2/1/6		NMR		1P1P	75
α-EIVA	C. ermineus	IV	30	6	7/2/1/7		NMR	5869	1PQR	76
Fold J: two cysteines, cystine stabilized turn
contryphan-R	C. radiatus		8	2	5		NMR		1QFB	47
contryphan-R [Δ1]			7	2	5		NMR		1DG0	45
contryphan-Sm	C. stercusmuscarum		8	2	5		NMR		1DFY, 1DFZ	38, 39
contryphan-Vn	C. ventricosus		9	2	5		NMR		1NXN	43
cyclic-contryphan			8	2	5		NMR		1D7T	37
conopressin-T	C. tulipa		9	2	4		NMR	20007		124
Fold K: no cysteine, fully helical
conantokin-G	C. geographus		17	0		B		NMR	1AD7, 1AWY, 1ONU	40, 41, 44
conantokin-T	C. tulipa		21	0				NMR	1ONT	42
Fold L: no cysteine, 3/10 helix and coil
conomarphin	C. marmoreus		15	0		M	NMR	7397	2YYF	115
conomarphin [d13>D]			15	0			NMR		2JQC	116

A brief description of the folds and sub-folds is provided in Figures 4a or 4b. The names of non-natural synthetic variants are indented in the case where the fold is the same as the wild-type conopeptide, whereas the name of the variant is preceded by an asterisk in the case where it adopts a different fold from the wild-type.

Only wild-type conopeptides are provided with a Conus (C.) species.

Cysteine frameworks are defined in Table 2.

The number of cysteine residues (# cysteines) is counted in the sequence of the mature peptide region in the precursor, before modification to cystines.

The “loop size” designates the length of the inter-cysteine segments defined in the cysteine frameworks, whose description is in Table 2.

“Method” refers to the experimental method used to determine the three-dimensional structures. If two different experimental methods were used for the same conopeptide, identifiers are provided on two separate lines.

The database identifiers in the Biological Magnetic Resonance dataBank (BMRB), Protein Data Bank (PDB) and ConoServer database are provided. Distinct structural studies are catalogued as different entries in ConoServer, and therefore each entry in ConoServer can be associated with a BMRB and/or a PDB entry. Some conopeptide three-dimensional structures are only found in ConoServer as they were not deposited by their authors in the PDB or BMRB.