1tno: Difference between revisions

Revision as of 16:15, 21 February 2008

Rat Protein Geranylgeranyltransferase Type-I Complexed with a GGPP analog and a KKKSKTKCVIM Peptide Derived from K-Ras4B

OverviewOverview

Post-translational modifications are essential for the proper function of many proteins in the cell. The attachment of an isoprenoid lipid (a process termed prenylation) by protein farnesyltransferase (FTase) or geranylgeranyltransferase type I (GGTase-I) is essential for the function of many signal transduction proteins involved in growth, differentiation, and oncogenesis. FTase and GGTase-I (also called the CaaX prenyltransferases) recognize protein substrates with a C-terminal tetrapeptide recognition motif called the Ca1a2X box. These enzymes possess distinct but overlapping protein substrate specificity that is determined primarily by the sequence identity of the Ca1a2X motif. To determine how the identity of the Ca1a2X motif residues and sequence upstream of this motif affect substrate binding, we have solved crystal structures of FTase and GGTase-I complexed with a total of eight cognate and cross-reactive substrate peptides, including those derived from the C termini of the oncoproteins K-Ras4B, H-Ras and TC21. These structures suggest that all peptide substrates adopt a common binding mode in the FTase and GGTase-I active site. Unexpectedly, while the X residue of the Ca1a2X motif binds in the same location for all GGTase-I substrates, the X residue of FTase substrates can bind in one of two different sites. Together, these structures outline a series of rules that govern substrate peptide selectivity; these rules were utilized to classify known protein substrates of CaaX prenyltransferases and to generate a list of hypothetical substrates within the human genome.

About this StructureAbout this Structure

1TNO is a Protein complex structure of sequences from Rattus norvegicus with , , and as ligands. Active as Protein geranylgeranyltransferase type I, with EC number 2.5.1.59 Full crystallographic information is available from OCA.

ReferenceReference

Crystallographic analysis of CaaX prenyltransferases complexed with substrates defines rules of protein substrate selectivity., Reid TS, Terry KL, Casey PJ, Beese LS, J Mol Biol. 2004 Oct 15;343(2):417-33. PMID:15451670

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OCA

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-[[Image:1tno.gif|left|200px]]<br /><applet load="1tno" size="450" color="white" frame="true" align="right" spinBox="true"
+[[Image:1tno.gif|left|200px]]<br /><applet load="1tno" size="350" color="white" frame="true" align="right" spinBox="true"
 caption="1tno, resolution 2.70&Aring;" />
 '''Rat Protein Geranylgeranyltransferase Type-I Complexed with a GGPP analog and a KKKSKTKCVIM Peptide Derived from K-Ras4B'''<br />
 ==Overview==
-Post-translational modifications are essential for the proper function of, many proteins in the cell. The attachment of an isoprenoid lipid (a, process termed prenylation) by protein farnesyltransferase (FTase) or, geranylgeranyltransferase type I (GGTase-I) is essential for the function, of many signal transduction proteins involved in growth, differentiation, and oncogenesis. FTase and GGTase-I (also called the CaaX, prenyltransferases) recognize protein substrates with a C-terminal, tetrapeptide recognition motif called the Ca1a2X box. These enzymes, possess distinct but overlapping protein substrate specificity that is, determined primarily by the sequence identity of the Ca1a2X motif. To, determine how the identity of the Ca1a2X motif residues and sequence, upstream of this motif affect substrate binding, we have solved crystal, structures of FTase and GGTase-I complexed with a total of eight cognate, and cross-reactive substrate peptides, including those derived from the C, termini of the oncoproteins K-Ras4B, H-Ras and TC21. These structures, suggest that all peptide substrates adopt a common binding mode in the, FTase and GGTase-I active site. Unexpectedly, while the X residue of the, Ca1a2X motif binds in the same location for all GGTase-I substrates, the X, residue of FTase substrates can bind in one of two different sites., Together, these structures outline a series of rules that govern substrate, peptide selectivity; these rules were utilized to classify known protein, substrates of CaaX prenyltransferases and to generate a list of, hypothetical substrates within the human genome.
+Post-translational modifications are essential for the proper function of many proteins in the cell. The attachment of an isoprenoid lipid (a process termed prenylation) by protein farnesyltransferase (FTase) or geranylgeranyltransferase type I (GGTase-I) is essential for the function of many signal transduction proteins involved in growth, differentiation, and oncogenesis. FTase and GGTase-I (also called the CaaX prenyltransferases) recognize protein substrates with a C-terminal tetrapeptide recognition motif called the Ca1a2X box. These enzymes possess distinct but overlapping protein substrate specificity that is determined primarily by the sequence identity of the Ca1a2X motif. To determine how the identity of the Ca1a2X motif residues and sequence upstream of this motif affect substrate binding, we have solved crystal structures of FTase and GGTase-I complexed with a total of eight cognate and cross-reactive substrate peptides, including those derived from the C termini of the oncoproteins K-Ras4B, H-Ras and TC21. These structures suggest that all peptide substrates adopt a common binding mode in the FTase and GGTase-I active site. Unexpectedly, while the X residue of the Ca1a2X motif binds in the same location for all GGTase-I substrates, the X residue of FTase substrates can bind in one of two different sites. Together, these structures outline a series of rules that govern substrate peptide selectivity; these rules were utilized to classify known protein substrates of CaaX prenyltransferases and to generate a list of hypothetical substrates within the human genome.
 ==About this Structure==
-TNO is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus] with ZN, CL, MES and MGM as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Protein_geranylgeranyltransferase_type_I Protein geranylgeranyltransferase type I], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.5.1.59 2.5.1.59] Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1TNO OCA].
+TNO is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus] with <scene name='pdbligand=ZN:'>ZN</scene>, <scene name='pdbligand=CL:'>CL</scene>, <scene name='pdbligand=MES:'>MES</scene> and <scene name='pdbligand=MGM:'>MGM</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Protein_geranylgeranyltransferase_type_I Protein geranylgeranyltransferase type I], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.5.1.59 2.5.1.59] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1TNO OCA].
 ==Reference==
@@ Line 14: / Line 14: @@
 [[Category: Protein geranylgeranyltransferase type I]]
 [[Category: Rattus norvegicus]]
-[[Category: Beese, L.S.]]
+[[Category: Beese, L S.]]
-[[Category: Casey, P.J.]]
+[[Category: Casey, P J.]]
-[[Category: Reid, T.S.]]
+[[Category: Reid, T S.]]
-[[Category: Terry, K.L.]]
+[[Category: Terry, K L.]]
 [[Category: CL]]
 [[Category: MES]]
@@ Line 33: / Line 33: @@
 [[Category: substrate selectivity]]
-''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Wed Nov 21 03:26:22 2007''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 15:15:28 2008''