Takashi Matsumoto

Chloranthalactone F, A sesquiterpenoid from the leaves of Chloranthus glaber

Abstract From the leaves of Chloranthus glaber Makino, a new sesquiterpenoid, chloranthalactone F was isolated together with the known compounds, chloranthalactones A, B and E, atractylenolide II and (−)-4β,7α-dihydroxyaromadendrane. The structure of the new compound was elucidated by spectroscopic methods.

Iridoid glucosides from the leaves and stems of Duranta erecta

From the leaves of Duranta erecta, four new iridoid glucosides, duranterectosides A, B, C and D, were isolated along with durantosides I and II, lamiide, lamiidoside and verbascoside. Duranterectoside A was also isolated from the stems together with durantosides I, II and III, and lamiidoside. The structures of the new compounds were elucidated based on the spectroscopic evidence.

Megastigmane glycosides from Salvia nemorosa

From the aerial parts of Salvia nemorosa, three new megastigmane glycosides, salvionosides A-C, were isolated, along with the known compounds, (6S,9R)- and (6S,9R)-roseosides, (6R,9R)- and (6R,9S)-3-oxo-alpha-ionol glucosides and blumeol C glucoside. The structures of the new compounds were elucidated on the basis of spectral and chemical evidence.

Orthosiphol D and E, minor diterpenes from Orthosiphon stamineus

Abstract From the aerial parts of Orthosiphon stamineus , two new diterpenes, orthosiphols D and E were isolated together with the known rosmarinic acid, sinensetin, scutellarein tetramethyl ether, salvigenin and orthosiphols A and B. The structures of the new compounds were elucidated mainly by spectroscopic methods.

Crystal structures of MKK4 kinase domain reveal that substrate peptide binds to an allosteric site and induces an auto-inhibition state

MKK4 activates both JNKs and p38s. We determined the crystal structures of human non-phosphorylated MKK4 kinase domain (npMKK4) complexed with AMP-PNP (npMKK4/AMP) and a ternary complex of npMKK4, AMP-PNP and p38α peptide (npMKK4/AMP/p38). These crystal structures revealed that the p38α peptide-bound npMKK4 at the allosteric site rather than at the putative substrate binding site and induced an auto-inhibition state. While the activation loop of the npMKK4/AMP complex was disordered, in the npMKK4/AMP/p38 complex it configured a long α-helix, which prevented substrate access to the active site and αC-helix movement to the active configuration of MKK4.

Nepetanudosides and iridoid glucosides having novel stereochemistry from Nepeta nuda ssp. Albiflora

From the aerial parts of Nepeta nuda ssp. albiflora, three new iridoid glucosides, nepetanudosides B, C and D, were isolated together with the known compound, velpetin. The structures of the new compounds were elucidated by spectral and chemical analyses.

5Z-7-Oxozeaenol covalently binds to MAP2K7 at Cys218 in an unprecedented manner.

5Z-7-Oxozeaenol (5Z7O) is a covalent bonding inhibitor against the several protein kinases (e.g., ERK2 and TAK1) that possess a free cysteine at the gatekeeper-2 position. In addition to this cysteine, MAP2K7 has three other cysteine residues that are candidate for covalent bonding by the inhibitor 5Z7O. The crystal structure of the MAP2K7/5Z7O complex revealed that the inhibitor binds to MAP2K7 at a cysteine residue located at the end of the hinge region and not at the gatekeeper-2 residue. The structural insights into the interaction of 5Z7O with MAP2K7 should aid the development of 5Z7O derivatives with improved potency and selectivity.

Diterpenoids having ent-kaurene and ent-spiro-seco-kaurene skeletons from Rabdosia longituba

Abstract Two new diterpenoids, rabdokaurins A and B, together with the known compounds, lasiokaurin, effusanin B, macrophyllin B, rabdophyllin G and exidonin were isolated from the aerial parts of Rabdosia longituba . The structures of the new compounds have been determined on the basis of the spectroscopic and chemical evidence.

Crystal structure of non-phosphorylated MAP2K6 in a putative auto-inhibition state

Mitogen-activated protein kinase kinase 6 (MAP2K6) plays a crucial role in the p38 MAP kinase signal cascade that regulates various stress-induced responses and is associated with pathological conditions. The crystal structure of human non-phosphorylated MAP2K6 (npMAP2K6) complexed with an ATP analogue was determined at 2.6 Å resolution and represents an auto-inhibition state of MAP2K6. Three characteristics of short α-helices configured in the activation loop region, termed activation helices (AH1, AH2 and AH3), are important in controlling the auto-inhibition mechanism. AH1 displaces the αC-helix, a component essential for forming the active configuration, away from the active site. AH1 and AH2 were found to enclose the γ-phosphate, the leaving group of ATP. A comparison with the related enzymes, MAP2K1 and MAP2K4 reveals that MAP2K6 has the unique auto-inhibition mechanism mediated by the three activation helices.

Longirabdolides A and B, 6,7-seco-ent-kaurenoids from Rabdosia longituba

From the aerial parts of Rabdosia longituba, three new diterpenes, longirabdolides E, F and G were isolated and the structures elucidated on the basis of the spectroscopic and chemical evidence.