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001-es BibID:	BIBFORM038085
Első szerző:	Li, Mi
Cím:	Structural and biochemical characterization of the inhibitor complexes of xenotropic murine leukemia virus-related virus protease / Li Mi, Gustchina Alla, Matúz Krisztina, Tözsér József, Namwong Sirilak, Goldfarb Nathan E., Dunn Ben M., Wlodawer Alexander
Dátum:	2011
ISSN:	1742-464X
Megjegyzések:	Interactions between the protease (PR) encoded by the xenotropic murine leukemia virus-related virus and a number of potential inhibitors have been investigated by biochemical and structural techniques. It was observed that several inhibitors used clinically against HIV PR exhibit nanomolar or even subnanomolar values of K(i) , depending on the exact experimental conditions. Both TL-3, a universal inhibitor of retroviral PRs, and some inhibitors originally shown to inhibit plasmepsins were also quite potent, whereas inhibition by pepstatin A was considerably weaker. Crystal structures of the complexes of xenotropic murine leukemia virus-related virus PR with TL-3, amprenavir and pepstatin A were solved at high resolution and compared with the structures of complexes of these inhibitors with other retropepsins. Whereas TL-3 and amprenavir bound in a predictable manner, spanning the substrate-binding site of the enzyme, two molecules of pepstatin A bound simultaneously in an unprecedented manner, leaving the catalytic water molecule in place.
Tárgyszavak:	Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban Molekuláris Medicina
Megjelenés:	Febs Journal. - 278 : 22 (2011), p. 4413-4424. -
További szerzők:	Gustchina, Alla Matúz Krisztina (1980-) (vegyész, biokémikus) Tőzsér József (1959-) (molekuláris biológus, biokémikus, vegyész) Namwong, Sirilak Goldfarb, Nathan E. Dunn, Ben M. Wlodawer, Alexander
Pályázati támogatás:	TÁMOP-4.2.1/B-09/1/KONV-2010-0007 TÁMOP Retrovirális biokémia
Internet cím:	DOI Intézményi repozitóriumban (DEA) tárolt változat
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001-es BibID:	BIBFORM038084
Első szerző:	Matúz Krisztina (vegyész, biokémikus)
Cím:	Inhibition of XMRV and HIV-1 proteases by pepstatin A and acetyl-pepstatin / Matúz Krisztina, Mótyán János András, Li Mi, Wlodawer Alexander, Tőzsér József
Dátum:	2012
Megjegyzések:	The kinetic properties of two classical inhibitors of aspartic proteases (PRs), pepstatin A and acetyl-pepstatin, were compared in their interactions with HIV-1 and xenotropic murine leukemia virus related virus (XMRV) PRs. Both compounds are substantially weaker inhibitors of XMRV PR than of HIV-1 PR. Previous kinetic and structural studies characterized HIV-1 PR-acetyl-pepstatin and XMRV PR-pepstatin A complexes and suggested dramatically different binding modes. Interaction energies were calculated for the possible binding modes and suggested a strong preference for the one-inhibitor binding mode for HIV-1 PR-acetyl-pepstatin and the two-inhibitor binding mode for XMRV PR-pepstatin A interactions. Comparison of the molecular models suggested that in the case of XMRV PR the relatively unfavorable interactions at S3' and the favorable interactions at S4 and S4' sites with the statine residues may shift the ground state binding towards the two-inhibitor binding mode, whereas the single molecule ground state binding of statines to the HIV-1 PR appear to be more favorable. The preferred single molecular binding to HIV-1 PR allows the formation of the transition state complex, represented by substantially better binding constants. Intriguingly, the crystal structure of the complex of acetyl-pepstatin with XMRV PR has shown a mixed type of binding: the unusual binding mode of two molecules of the inhibitor to the enzyme, in a mode very similar to the previously determined complex with pepstatin A, together with the classical binding mode found for HIV-1 PR. The structure is thus in good agreement with the very similar interaction energies calculated for the two types of binding.
Tárgyszavak:	Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban XMRV protease
Megjelenés:	FEBS Journal. - 279 : 17 (2012), p. 3276-3286. -
További szerzők:	Mótyán János András (1981-) (biokémikus, molekuláris biológus) Li, Mi Wlodawer, Alexander Tőzsér József (1959-) (molekuláris biológus, biokémikus, vegyész)
Internet cím:	DOI Intézményi repozitóriumban (DEA) tárolt változat
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