1yf8: Difference between revisions

Revision as of 17:04, 21 February 2008

Crystal structure of Himalayan mistletoe RIP reveals the presence of a natural inhibitor and a new functionally active sugar-binding site

OverviewOverview

Ribosome-inactivating proteins (RIPs) are toxins involved in plant defense. How the plant prevents autotoxicity is not yet fully understood. The present study is the first structural evidence of a naturally inhibited form of RIP from a plant. Himalayan mistletoe RIP (HmRIP) was purified from Viscum album leaves and crystallized with lactose. The structure was determined by the molecular replacement method and refined at 2.8-A resolution. The crystal structure revealed the presence of high quality non-protein electron density at the active site, into which a pteridine derivative (2-amino 4-isopropyl 6-carboxyl pteridine) was modeled. The carboxyl group of the ligand binds strongly with the key active site residue Arg(162), nullifies the positive charge required for catalysis, and thereby acts as a natural inhibitor. Lectin subunits of RIPs have two active sugar-binding sites present in 1alpha- and 2gamma-subdomains. A third functionally active site has been identified in the 1beta-subdomain of HmRIP. The 1beta-site is active despite the absence of conserved polar sugar-binding residues. Loss of these residues is compensated by the following: (i) the presence of an extended site where the penultimate sugar also interacts with the protein; (ii) the interactions of galactose with the protein main chain carbonyl and amide nitrogen atoms; (iii) the presence of a well defined pocket encircled by four walls; and (iv) a favorable stacking of the galactose ring with Tyr(66) besides the conserved Phe(75). The mode of sugar binding is also distinct at the 1alpha and 2gamma sugar-binding sites.

About this StructureAbout this Structure

1YF8 is a Protein complex structure of sequences from Viscum album with , and as ligands. Active as rRNA N-glycosylase, with EC number 3.2.2.22 Full crystallographic information is available from OCA.

ReferenceReference

Crystal structure of himalayan mistletoe ribosome-inactivating protein reveals the presence of a natural inhibitor and a new functionally active sugar-binding site., Mishra V, Bilgrami S, Sharma RS, Kaur P, Yadav S, Krauspenhaar R, Betzel C, Voelter W, Babu CR, Singh TP, J Biol Chem. 2005 May 27;280(21):20712-21. Epub 2005 Mar 17. PMID:15774467

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OCA

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-[[Image:1yf8.gif|left|200px]]<br /><applet load="1yf8" size="450" color="white" frame="true" align="right" spinBox="true"
+[[Image:1yf8.gif|left|200px]]<br /><applet load="1yf8" size="350" color="white" frame="true" align="right" spinBox="true"
 caption="1yf8, resolution 2.80&Aring;" />
 '''Crystal structure of Himalayan mistletoe RIP reveals the presence of a natural inhibitor and a new functionally active sugar-binding site'''<br />
 ==Overview==
-Ribosome-inactivating proteins (RIPs) are toxins involved in plant, defense. How the plant prevents autotoxicity is not yet fully understood., The present study is the first structural evidence of a naturally, inhibited form of RIP from a plant. Himalayan mistletoe RIP (HmRIP) was, purified from Viscum album leaves and crystallized with lactose. The, structure was determined by the molecular replacement method and refined, at 2.8-A resolution. The crystal structure revealed the presence of high, quality non-protein electron density at the active site, into which a, pteridine derivative (2-amino 4-isopropyl 6-carboxyl pteridine) was, modeled. The carboxyl group of the ligand binds strongly with the key, active site residue Arg(162), nullifies the positive charge required for, catalysis, and thereby acts as a natural inhibitor. Lectin subunits of, RIPs have two active sugar-binding sites present in 1alpha- and, 2gamma-subdomains. A third functionally active site has been identified in, the 1beta-subdomain of HmRIP. The 1beta-site is active despite the absence, of conserved polar sugar-binding residues. Loss of these residues is, compensated by the following: (i) the presence of an extended site where, the penultimate sugar also interacts with the protein; (ii) the, interactions of galactose with the protein main chain carbonyl and amide, nitrogen atoms; (iii) the presence of a well defined pocket encircled by, four walls; and (iv) a favorable stacking of the galactose ring with, Tyr(66) besides the conserved Phe(75). The mode of sugar binding is also, distinct at the 1alpha and 2gamma sugar-binding sites.
+Ribosome-inactivating proteins (RIPs) are toxins involved in plant defense. How the plant prevents autotoxicity is not yet fully understood. The present study is the first structural evidence of a naturally inhibited form of RIP from a plant. Himalayan mistletoe RIP (HmRIP) was purified from Viscum album leaves and crystallized with lactose. The structure was determined by the molecular replacement method and refined at 2.8-A resolution. The crystal structure revealed the presence of high quality non-protein electron density at the active site, into which a pteridine derivative (2-amino 4-isopropyl 6-carboxyl pteridine) was modeled. The carboxyl group of the ligand binds strongly with the key active site residue Arg(162), nullifies the positive charge required for catalysis, and thereby acts as a natural inhibitor. Lectin subunits of RIPs have two active sugar-binding sites present in 1alpha- and 2gamma-subdomains. A third functionally active site has been identified in the 1beta-subdomain of HmRIP. The 1beta-site is active despite the absence of conserved polar sugar-binding residues. Loss of these residues is compensated by the following: (i) the presence of an extended site where the penultimate sugar also interacts with the protein; (ii) the interactions of galactose with the protein main chain carbonyl and amide nitrogen atoms; (iii) the presence of a well defined pocket encircled by four walls; and (iv) a favorable stacking of the galactose ring with Tyr(66) besides the conserved Phe(75). The mode of sugar binding is also distinct at the 1alpha and 2gamma sugar-binding sites.
 ==About this Structure==
-YF8 is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Viscum_album Viscum album] with NAG, GAL and P6C as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/rRNA_N-glycosylase rRNA N-glycosylase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.2.2.22 3.2.2.22] Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1YF8 OCA].
+YF8 is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Viscum_album Viscum album] with <scene name='pdbligand=NAG:'>NAG</scene>, <scene name='pdbligand=GAL:'>GAL</scene> and <scene name='pdbligand=P6C:'>P6C</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/rRNA_N-glycosylase rRNA N-glycosylase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.2.2.22 3.2.2.22] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1YF8 OCA].
 ==Reference==
@@ Line 14: / Line 14: @@
 [[Category: Viscum album]]
 [[Category: rRNA N-glycosylase]]
-[[Category: Babu, C.R.]]
+[[Category: Babu, C R.]]
 [[Category: Betzel, C.]]
 [[Category: Bilgrami, S.]]
 [[Category: Kaur, P.]]
 [[Category: Mishra, V.]]
-[[Category: Sharma, R.S.]]
+[[Category: Sharma, R S.]]
-[[Category: Singh, T.P.]]
+[[Category: Singh, T P.]]
 [[Category: Yadav, S.]]
 [[Category: GAL]]
@@ Line 32: / Line 32: @@
 [[Category: viscum album]]
-''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Wed Nov 21 06:43:53 2007''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:04:49 2008''