1h1h: Difference between revisions

Revision as of 13:56, 21 February 2008

CRYSTAL STRUCTURE OF EOSINOPHIL CATIONIC PROTEIN IN COMPLEX WITH 2',5'-ADP AT 2.0 A RESOLUTION REVEALS THE DETAILS OF THE RIBONUCLEOLYTIC ACTIVE SITE

OverviewOverview

Eosinophil cationic protein (ECP) is a component of the eosinophil granule matrix. It shows marked toxicity against helminth parasites, bacteria single-stranded RNA viruses, and host epithelial cells. Secretion of human ECP is related to eosinophil-associated allergic, asthmatic, and inflammatory diseases. ECP belongs to the pancreatic ribonuclease superfamily of proteins, and the crystal structure of ECP in the unliganded form (determined previously) exhibited a conserved RNase A fold [Boix, E., et al. (1999) Biochemistry 38, 16794-16801]. We have now determined a high-resolution (2.0 A) crystal structure of ECP in complex with adenosine 2',5'-diphosphate (2',5'-ADP) which has revealed the details of the ribonucleolytic active site. Residues Gln-14, His-15, and Lys-38 make hydrogen bond interactions with the phosphate at the P(1) site, while His-128 interacts with the purine ring at the B(2) site. A new phosphate binding site, P(-)(1), has been identified which involves Arg-34. This study is the first detailed structural analysis of the nucleotide recognition site in ECP and provides a starting point for the understanding of its substrate specificity and low catalytic efficiency compared with that of the eosinophil-derived neurotoxin (EDN), a close homologue.

About this StructureAbout this Structure

1H1H is a Single protein structure of sequence from Homo sapiens with as ligand. Known structural/functional Site: . Full crystallographic information is available from OCA.

ReferenceReference

The crystal structure of eosinophil cationic protein in complex with 2',5'-ADP at 2.0 A resolution reveals the details of the ribonucleolytic active site., Mohan CG, Boix E, Evans HR, Nikolovski Z, Nogues MV, Cuchillo CM, Acharya KR, Biochemistry. 2002 Oct 8;41(40):12100-6. PMID:12356310

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 ==Overview==
-Eosinophil cationic protein (ECP) is a component of the eosinophil granule, matrix. It shows marked toxicity against helminth parasites, bacteria, single-stranded RNA viruses, and host epithelial cells. Secretion of human, ECP is related to eosinophil-associated allergic, asthmatic, and, inflammatory diseases. ECP belongs to the pancreatic ribonuclease, superfamily of proteins, and the crystal structure of ECP in the, unliganded form (determined previously) exhibited a conserved RNase A fold, [Boix, E., et al. (1999) Biochemistry 38, 16794-16801]. We have now, determined a high-resolution (2.0 A) crystal structure of ECP in complex, with adenosine 2',5'-diphosphate (2',5'-ADP) which has revealed the, details of the ribonucleolytic active site. Residues Gln-14, His-15, and, Lys-38 make hydrogen bond interactions with the phosphate at the P(1), site, while His-128 interacts with the purine ring at the B(2) site. A new, phosphate binding site, P(-)(1), has been identified which involves, Arg-34. This study is the first detailed structural analysis of the, nucleotide recognition site in ECP and provides a starting point for the, understanding of its substrate specificity and low catalytic efficiency, compared with that of the eosinophil-derived neurotoxin (EDN), a close, homologue.
+Eosinophil cationic protein (ECP) is a component of the eosinophil granule matrix. It shows marked toxicity against helminth parasites, bacteria single-stranded RNA viruses, and host epithelial cells. Secretion of human ECP is related to eosinophil-associated allergic, asthmatic, and inflammatory diseases. ECP belongs to the pancreatic ribonuclease superfamily of proteins, and the crystal structure of ECP in the unliganded form (determined previously) exhibited a conserved RNase A fold [Boix, E., et al. (1999) Biochemistry 38, 16794-16801]. We have now determined a high-resolution (2.0 A) crystal structure of ECP in complex with adenosine 2',5'-diphosphate (2',5'-ADP) which has revealed the details of the ribonucleolytic active site. Residues Gln-14, His-15, and Lys-38 make hydrogen bond interactions with the phosphate at the P(1) site, while His-128 interacts with the purine ring at the B(2) site. A new phosphate binding site, P(-)(1), has been identified which involves Arg-34. This study is the first detailed structural analysis of the nucleotide recognition site in ECP and provides a starting point for the understanding of its substrate specificity and low catalytic efficiency compared with that of the eosinophil-derived neurotoxin (EDN), a close homologue.
 ==About this Structure==
@@ Line 13: / Line 13: @@
 [[Category: Homo sapiens]]
 [[Category: Single protein]]
-[[Category: Acharya, K.R.]]
+[[Category: Acharya, K R.]]
 [[Category: Boix, E.]]
-[[Category: Cuchillo, C.M.]]
+[[Category: Cuchillo, C M.]]
-[[Category: Evans, H.R.]]
+[[Category: Evans, H R.]]
-[[Category: Mohan, C.G.]]
+[[Category: Mohan, C G.]]
 [[Category: Nikolovski, Z.]]
-[[Category: Nogues, M.V.]]
+[[Category: Nogues, M V.]]
 [[Category: A2P]]
 [[Category: 5'-diphosphate]]
@@ Line 28: / Line 28: @@
 [[Category: toxin]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Feb  3 09:45:08 2008''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 12:56:18 2008''