Berberine potently inhibits protein tyrosine phosphatase 1B: Investigation by docking simulation and experimental validation

Figures & data

Figure 1 Structure of berberine.

Figure 2 Structure of Pnu177496.

Figure 3 (A) Perspective cartoon view of h-PTP 1B co-crystallized with Pnu177496 (in red). (B) Cartoon view of the h-PTP 1B showing the binding pocket as dotted red area.

Table I.  the score values for each molecular pose suggested by the LigandFit® docking engine.

	Scoring Functions
Pose	Ligscore 1	Ligscore 2	-PLP1	-PLP2	JAIN	-PMF	LUDI	Consensus Score
1	3.87	4.46	64.74	64.1	− 0.33	73.19	473	7
2	3.57	3.69	47.99	49.83	− 0.98	83.00	416	6
3	2.62	4.14	55.38	53.1	− 0.93	69.38	538	5
4	3.20	2.59	32.85	39.06	− 0.81	61.71	400	4
5	3.97	3.30	39.44	42.67	− 0.97	42.77	392	3
6	2.93	3.58	37.87	35.37	− 0.8	40.31	336	2
7	1.93	3.41	38.58	38.14	− 0.01	46.37	285	1
8	2.44	3.47	35.8	39.13	− 0.83	54.99	353	0
9	2.37	3.43	19.06	17.46	− 1.73	44.48	259	0
10	1.22	3.29	34.95	35.51	− 1.23	38.94	266	0
11	1.74	3.08	24.61	26.06	− 2.06	11.71	143	0

Figure 4 The highest ranking binding mode of berberine as suggested by the consensus scoring function. (A) Berberine structure docked into the water accessible surface (Connolly's surface) within the binding pocket of h-PTP 1B. The surface is represented as yellow dotted cavity (B) Perspective cartoon view of h-PTP 1B and the docked berberine structure (in red).

Figure 5 Detailed view of the docked berberine structure and the corresponding interacting amino-acid moieties within the binding site of h-PTP 1B.

Figure 6 The highest ranking binding mode of inhibitor Pnu177496 as suggested by our docking-scoring conditions. (A) Detailed view of the docked structure and the corresponding interacting amino-acids. (B) Comparison between the docked conformer/pose of inhibitor Pnu177496 (green) as produced by the docking simulation and the crystallographic structure of this inhibitor within h-PTP 1B (red, PDB code: 1g7f)

Figure 7 The effect of variable berberine concentrations on the relative activity of h-PTP 1B. Data are expressed as means of three replicates ± standard deviation of measurements.

Figure 8 A Lineweaver-Burk plot of berberine inhibition of h-PTP 1B. The inhibition kinetics were determined at various fixed concentrations of berberine: 0 nM (•), 60 nM (▪), 110 nM (▴). Each point represents the average of three replicates.