Molecular dynamics simulations of the structure of aldose reductase complexed with the inhibitor Tolrestat

Rastelli, Giulio; Costantino, Luca

doi:10.1016/S0960-894X(98)00083-3

This study reports a molecular dynamics (MD) investigation on the structure of aldose reductase (ALR2) complexed with the potent inhibitor tolrestat. The simulations predict four different orientations of tolrestat into the ALR2 binding site; these orientations have in common a strong interaction of the anionic carboxylate with Tyr48, His110, Trp111 and NADP+, but completely differ for the orientation of the aromatic portion of the inhibitor. Interestingly, the orientation in which tolrestat gives the most attractive interaction energy with the enzyme is in full accord with the x-ray crystal structure of the complex that has been reported in the literature after this work was completed. In addition, the suggestion of more than one orientation of tolrestat during MD is in agreement with recent electrospray mass spectrometry experiments on the ALR2-tolrestat complex.

Molecular dynamics simulations of the structure of aldose reductase complexed with the inhibitor Tolrestat / Rastelli, Giulio; Costantino, Luca. - In: BIOORGANIC & MEDICINAL CHEMISTRY LETTERS. - ISSN 0960-894X. - STAMPA. - 8(1998), pp. 641-646.

Data di pubblicazione:	1998
Titolo:	Molecular dynamics simulations of the structure of aldose reductase complexed with the inhibitor Tolrestat
Autore/i:	Rastelli, Giulio; Costantino, Luca
Autore/i UNIMORE:	RASTELLI, Giulio COSTANTINO, Luca
Digital Object Identifier (DOI):	http://dx.doi.org/10.1016/S0960-894X(98)00083-3
Rivista:	BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
Volume:	8
Pagina iniziale:	641
Pagina finale:	646
Codice identificativo ISI:	WOS:000072733000016
Codice identificativo Scopus:	2-s2.0-0032539837
Codice identificativo Pubmed:	9871575
Citazione:	Molecular dynamics simulations of the structure of aldose reductase complexed with the inhibitor Tolrestat / Rastelli, Giulio; Costantino, Luca. - In: BIOORGANIC & MEDICINAL CHEMISTRY LETTERS. - ISSN 0960-894X. - STAMPA. - 8(1998), pp. 641-646.
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http://hdl.handle.net/11380/458205

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