TY  - JOUR
A1  - Fotie, J.
A1  - Nkengfack, A. E.
A1  - Peter, Martin G.
A1  - Heydenreich, Matthias
A1  - Fomum, Z. T.
T1  - Chemical constituents of the ethyl acetate extracts of the stem bark and fruits of Dichrostachys cinerea and the roots of Parkia bicolor
N2  - The antibacterial activities of ethyl acetate, methanol and aqueous extracts of the stem bark of Dichrostachys cinerea and the roots of Parkia bicolor have been evaluated. Ethyl acetate extracts have been investigated, studies that led to a series of known compounds, amongst which many are reported here for the very first time from both the species
Y1  - 2004
SN  - 1011-3924
ER  - 
TY  - JOUR
A1  - Vaaje-Kolstad, G.
A1  - Vasella, A.
A1  - Peter, Martin G.
A1  - Netter, C.
A1  - Houston, Douglas R.
A1  - Westereng, B.
A1  - Synstad, Bjoenar
A1  - Eijsink, Vincent G. H.
A1  - van Aalten, Daan M. F.
T1  - Interactions of a family 18 chitinase with the designed inhibitor HM508 and its degradation product, chitobiono- delta-lactone
N2  - We describe enzymological and structural analyses of the interaction between the family 18 chitinase ChiB from Serratia marcescens and the designed inhibitor N,N'-diacetylchitobionoxime-N-phenylcarbamate (HM508). HM508 acts as a competitive inhibitor of this enzyme with a K-i in the 50 muM range. Active site mutants of ChiB show K-i values ranging from 1 to 200 muM, providing insight into some of the interactions that determine inhibitor affinity. Interestingly, the wild type enzyme slowly degrades HM508, but the inhibitor is essentially stable in the presence of the moderately active D142N mutant of ChiB. The crystal structure of the D142N-HM508 complex revealed that the two sugar moieties bind to the -2 and -1 subsites, whereas the phenyl group interacts with aromatic side chains that line the +1 and +2 subsites. Enzymatic degradation of HM508, as well as a Trp-->Ala mutation in the +2 subsite of ChiB, led to reduced affinity for the inhibitor, showing that interactions between the phenyl group and the enzyme contribute to binding. Interestingly, a complex of enzymatically degraded HM508 with the wild type enzyme showed a chitobiono-delta- lactone bound in the -2 and -1 subsites, despite the fact that the equilibrium between the lactone and the hydroxy acid forms in solution lies far toward the latter. This shows that the active site preferentially binds the E-4 conformation of the -1 sugar, which resembles the proposed transition state of the reaction
Y1  - 2004
SN  - 0021-9258
ER  - 
TY  - JOUR
A1  - Vaaje-Kolstad, G.
A1  - Houston, Douglas R.
A1  - Rao, F. V.
A1  - Peter, Martin G.
A1  - Synstad, Bjoenar
A1  - van Aalten, Daan M. F.
A1  - Eijsink, Vincent G. H.
T1  - Structure of the D142N mutant of the family 18 chitinase ChiB from Serratia marcescens and its complex with allosamidin
N2  - Catalysis by ChiB, a family 18 chitinase from Serratia marcescens, involves a conformational change of Asp142 which is part of a characteristic D140XD142XE144 sequence motif In the free enzyme Asp142 points towards Asp140, whereas it rotates towards the catalytic acid, Glu144, upon ligand binding. Mutation of Asp142 to Asn reduced k(cat) and affinity for allosamidin, a competitive inhibitor. The X-ray structure of the D142N mutant showed that Asn142 points towards Glu144 in the absence of a ligand. The active site also showed other structural adjustments (Tyr10, Ser93) that had previously been observed in the wild-type enzyme upon substrate binding. The X-ray structure of a complex of D142N with allosamidin, a pseudotrisaccharide competitive inhibitor, was essentially identical to that of the wild-type enzyme in complex with the same compound. Thus, the reduced allosamidin affinity in the mutant is not caused by structural changes but solely by the loss of electrostatic interactions with Asp142. The importance of electrostatics was further confirmed by the pH dependence of catalysis and allosamidin inhibition. The pH-dependent apparent affinities for allosamidin were not correlated with k(cat), indicating that it is probably better to view the inhibitor as a mimic of the oxazolinium ion reaction intermediate than as a transition state analogue. (C) 2003 Elsevier B.V. All rights reserved
Y1  - 2004
SN  - 1570-9639
ER  - 
TY  - JOUR
A1  - Yenesew, Abiy
A1  - Induli, M.
A1  - Derese, Solomon
A1  - Midiwo, Jacob O.
A1  - Heydenreich, Matthias
A1  - Peter, Martin G.
A1  - Akala, Hoseah M.
A1  - Wangui, Julia
A1  - Liyala, Pamela
A1  - Waters, Norman C.
T1  - Anti-plasmodial flavonoids from the stem bark of Erythrina abyssinica
N2  - The ethyl acetate extract of the stem bark of Erythrina abyssinica showed anti-plasmodial activity against the chloroquine-sensitive (D6) and chloroquine-resistant (W2) strains of Plasmodium falciparum with IC50 values of 7.9 +/- 1.1 and 5.3 +/- 0.7 mug/ml, respectively. From this extract, a new chalcone, 2,3,4,4'-tetrahydroxy-5- prenylchalcone (trivial name 5-prenylbutein) and a new flavanone, 4',7-dihydroxy-3'-methoxy-5'- prenylflavanone (trivial name, 5-deoxyabyssinin II) along with known flavonoids have been isolated as the anti- plasmodial principles. The structures were determined on the basis of spectroscopic evidence. (C) 2004 Elsevier Ltd. All rights reserved
Y1  - 2004
SN  - 0031-9422
ER  -