1d8v

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==Overview==
==Overview==
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We present the solution structure of MAP30, a plant protein with anti-HIV, and anti-tumor activities. Structural analysis and subsequent biochemical, assays lead to several novel discoveries. First, MAP30 acts like a DNA, glycosylase/apurinic (ap) lyase, an additional activity distinct from its, known RNA N-glycosidase activity toward the 28S rRNA. Glycosylase/ap lyase, activity explains MAP30's apparent inhibition of the HIV-1 integrase, MAP30's ability to irreversibly relax supercoiled DNA, and may be an, alternative cytotoxic pathway that contributes to MAP30's, anti-HIV/anti-tumor activities. Second, two distinct, but contiguous, subsites are responsible for MAP30's glycosylase/ap lyase activity. Third, Mn2+ and Zn2+ interact with negatively charged surfaces next to the, catalytic sites, facilitating DNA substrate binding instead of directly, participating in catalysis.
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We present the solution structure of MAP30, a plant protein with anti-HIV and anti-tumor activities. Structural analysis and subsequent biochemical assays lead to several novel discoveries. First, MAP30 acts like a DNA glycosylase/apurinic (ap) lyase, an additional activity distinct from its known RNA N-glycosidase activity toward the 28S rRNA. Glycosylase/ap lyase activity explains MAP30's apparent inhibition of the HIV-1 integrase, MAP30's ability to irreversibly relax supercoiled DNA, and may be an alternative cytotoxic pathway that contributes to MAP30's anti-HIV/anti-tumor activities. Second, two distinct, but contiguous, subsites are responsible for MAP30's glycosylase/ap lyase activity. Third, Mn2+ and Zn2+ interact with negatively charged surfaces next to the catalytic sites, facilitating DNA substrate binding instead of directly participating in catalysis.
==About this Structure==
==About this Structure==
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[[Category: Neamati, N.]]
[[Category: Neamati, N.]]
[[Category: Palmer, I.]]
[[Category: Palmer, I.]]
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[[Category: Stahl, S.J.]]
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[[Category: Stahl, S J.]]
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[[Category: Wang, Y.X.]]
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[[Category: Wang, Y X.]]
[[Category: single chain]]
[[Category: single chain]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri Feb 15 15:39:00 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 12:14:10 2008''

Revision as of 10:14, 21 February 2008


1d8v

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THE RESTRAINED AND MINIMIZED AVERAGE NMR STRUCTURE OF MAP30.

Overview

We present the solution structure of MAP30, a plant protein with anti-HIV and anti-tumor activities. Structural analysis and subsequent biochemical assays lead to several novel discoveries. First, MAP30 acts like a DNA glycosylase/apurinic (ap) lyase, an additional activity distinct from its known RNA N-glycosidase activity toward the 28S rRNA. Glycosylase/ap lyase activity explains MAP30's apparent inhibition of the HIV-1 integrase, MAP30's ability to irreversibly relax supercoiled DNA, and may be an alternative cytotoxic pathway that contributes to MAP30's anti-HIV/anti-tumor activities. Second, two distinct, but contiguous, subsites are responsible for MAP30's glycosylase/ap lyase activity. Third, Mn2+ and Zn2+ interact with negatively charged surfaces next to the catalytic sites, facilitating DNA substrate binding instead of directly participating in catalysis.

About this Structure

1D8V is a Single protein structure of sequence from Momordica charantia. Full crystallographic information is available from OCA.

Reference

Solution structure of anti-HIV-1 and anti-tumor protein MAP30: structural insights into its multiple functions., Wang YX, Neamati N, Jacob J, Palmer I, Stahl SJ, Kaufman JD, Huang PL, Huang PL, Winslow HE, Pommier Y, Wingfield PT, Lee-Huang S, Bax A, Torchia DA, Cell. 1999 Nov 12;99(4):433-42. PMID:10571185

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