Structural basis for the hydrolysis of ATP by a nucleotide binding subunit of an amino acid ABC transporter from Thermus thermophilus.

ATP-binding cassette (ABC) transporters are a major family of small molecule transporter proteins, and their deregulation is associated with several diseases, including cancer. Here, we report the crystal structure of the nucleotide binding domain (NBD) of an amino acid ABC transporter from Thermus thermophilus (TTHA1159) in its apo form and as a complex with ADP along with functional studies. TTHA1159 is a putative arginine ABC transporter. The apo-TTHA1159 was crystallized in dimeric form, a hitherto unreported form of an apo NBD. Structural comparison of the apo and ADP-Mg(2+) complexes revealed that Phe14 of TTHA1159 undergoes a significant conformational change to accommodate ADP, and that the bound ADP interacts with the P-loop (Gly40-Thr45). Modeling of ATP-Mg(2+):TTHA1159 complex revealed that Gln86 and Glu164 are involved in water-mediated hydrogen bonding contacts and Asp163 in Mg(2+) ion-mediated hydrogen bonding contacts with the γ-phosphate of ATP, consistent with the findings of other ABC transporters. Mutational studies confirmed the necessity of each of these residues, and a comparison of the apo/ADP Mg(2+):TTHA1159 with its ATP-complex model suggests the likelihood of a key conformational change to the Gln86 side chain for ATP hydrolysis.

Phytochemical analyses and activity of herbal medicinal plants of North- East India for anti-diabetic, anti-cancer and anti-tuberculosis and their docking studies.

The traditional knowledge of medicinal plants that are in use by the indigenous Jaintia tribes residing in few isolated pockets of North-East India is documented here. The present study was carried out through the personal discussion with the president of the Jaintia Indigenous Herbal Medicine Association, Dr.H.Carehome Pakyntein from Jowai, Meghalaya. The plants being used generation after generation by his family of herbalists to cure ailments like tuberculosis, cancer and diabetes were selected for the present study. In order to scientifically validate the use of these selected plants for the cure of selected diseases, phytochemical analyses, characterization and molecular docking studies of some of the selected compounds from these plants have been carried out. The compounds 2-hydroxy-4-methoxy- Benzaldehyde from methanolic extract of Strophanthus Wallichii and DL tetrahydropalmatine from Stephania Hernandifolia have been confirmed after determining their molecular structures, justifying the activity of these two plants against TB and cancer, respectively. The present study covers the potentials of some of the medicinal plants of North east India in curing common diseases due to which millions of people suffer and die. The presence of certain compounds in these plants related to the cure of the diseases deserves further studies.

2-Methyl-4-(naphthalen-2-yl)-3a-nitro-3,3a,4,9b-tetra-hydro-2H-spiro-[chromeno[3,4-c]pyrrole-1,3'-indolin]-2'-one.

In the title compound, C29H23N3O4, the 2-methylpyrrolidine ring adopts a twist conformation on the N-C bond involving the spiro C atom, while the hydropyran ring adopts an envelope conformation with the methine C atom bonded to the O atom as the flap. The mean plane of the indoline-2-one ring system is almost perpendicular to the mean plane of the pyrrolidine ring, making a dihedral angle of 89.73 (8)°. The latter ring makes dihedral angles of 47.80 (8) with the naphthalene ring system and 32.38 (8)° with the hydropyran ring mean plane. There is an intra-molecular C-H⋯O hydrogen bond involving the indoline-2-one O atom. In the crystal, adjacent mol-ecules are linked via N-H⋯O hydrogen bonds, forming chains propagating along [100]. The chains are linked via weak C-H⋯O hydrogen bonds, forming two-dimensional networks, lying parallel to (101), and consolidated by C-H⋯π inter-actions.

6-(4-Meth-oxy-phen-yl)-6a-nitro-6,6a,6b,7,8,9,10,12a-octa-hydro-spiro-[chromeno[3,4-a]indolizine-12,3'-indolin]-2'-one.

In the title compound, C29H27N3O5, the hydropyran ring adopts an envelope conformation with the methine C atom bearing the para-meth-oxy-benzene ring as the flap. The central pyrrolidine ring has a twist conformation on the N-C bond involving the spiro C atom. The piperidine ring adopts a chair conformation. An intra-molecular C-H⋯O contact closes an S(7) ring. In the crystal, inversion dimers linked by C-H⋯O inter-actions generate R 2 (2)(18) loops and N-H⋯O hydrogen bonds connect the dimers into [100] chains.

8,13,26-Trioxa-23-thia-21-aza-penta-cyclo-[18.6.0.0(2,7).0(14,19).0(21,25)]hexa-cosa-2(7),3,5,14,16,18-hexa-ene.

In the title compound, C21H23NO3S, both the thia-zole and oxazolidine rings adopt twist conformations. The mean plane of the thia-zole ring makes a dihedral angle of 61.02 (7)° with the oxazolidine ring mean plane, and dihedral angles of 22.72 (6) and 75.07 (6)° with the benzene rings. The benzene rings are almost perpendicular to one another, making a dihedral angle of 89.14 (6)°. There are bifurcated intra-molecular C-H⋯O hydrogen bonds in the mol-ecular structure. In the crystal, mol-ecules are linked via C-H⋯π inter-actions, forming chains propagating along [100].

8,11,24-Trioxa-21-thia-19-aza-penta-cyclo-[16.6.0.0(2,7).0(12,17).0(19,23)]tetra-cosa-2(7),3,5,12,14,16-hexa-ene.

In the title compound, C19H19NO3S, the thia-zole and oxazolidine rings each adopt an envelope conformation, with the S and O atoms as the respective flap atoms. The thia-zole and oxazolidine rings (all atoms) make a dihedral angle of 66.39 (11)° while the phenyl rings subtend a dihedral angle of 22.71 (10)°.

6a-Nitro-6-phenyl-6,6a,6b,7,8,9,10,12a-octa-hydro-spiro-[chromeno[3,4-a]indol-izine-12,3'-indolin]-2'-one.

In the title compound, C28H25N3O4, the central pyrrolidine ring adopts adopts an envelope conformation with the N atom as the flap and the piperidine ring adopts a chair conformation. The pendant pyrrolidine ring is almost planar (r.m.s. deviation = 0.008 Å). An intra-molecular C-H⋯O inter-action closes an S(6) ring. In the crystal, inversion dimers linked by pairs of N-H⋯O hydrogen bonds generate R 2 (2)(8) loops.

(1S,3'S,3a'R,6'S)-6'-(2-Chloro-phen-yl)-3'-[(2R,3S)-1-(4-meth-oxy-phen-yl)-4-oxo-3-phenyl-azetidin-2-yl]-2-oxo-3',3'a,4',6'-tetra-hydro-2H,2'H-spiro-[ace-naphthyl-ene-1,1'-pyrrolo-[1,2-c][1,3]thia-zole]-2',2'-dicarbo-nitrile.

The mol-ecular conformation of the title compound, C41H29ClN4O3S, is stabilized by intra-molecular C-H⋯O and C-H⋯Cl hydrogen bonds. The thia-zole ring adopts an envelope conformation with the N atom as the flap, while the pyrrolidine ring has a twisted conformation on the N-C bond involving the spiro C atom. The ß la-ctam ring makes dihedral angles of 39.74 (15) and 16.21 (16)° with the mean planes of the thia-zole and pyrrolidine rings, respectively. The thia-zole ring mean plane makes dihedral angles of 23.79 (13) and 70.88 (13) ° with the pyrrolidine and cyclo-pentane rings, respectively, while the pyrrolidine ring makes a dihedral angle of 85.63 (13)° with the cyclo-pentane ring. The O atom attached to the ß la-ctam ring deviates from its mean plane by 0.040 (2) Å, while the O atom attached to the cyclo-pentane ring deviates from its mean plane by 0.132 (2) Å. In the crystal, mol-ecules are linked by C-H⋯O hydrogen bonds, forming chains along [010], and C-H⋯π and π-π inter-actions [centroid-centroid distance = 3.6928 (17) Å].