2o3e: Difference between revisions

Revision as of 03:18, 28 July 2008

This article has been automatically seeded. Changes to this page should pertain to the PDB entry only and not to the protein or biomolecule in general.

File:2o3e.png

Template:STRUCTURE 2o3e

Crystal structure of engineered neurolysin with thimet oligopeptidase specificity for neurotensin cleavage site.Crystal structure of engineered neurolysin with thimet oligopeptidase specificity for neurotensin cleavage site.

Template:ABSTRACT PUBMED 17251185

About this StructureAbout this Structure

2O3E is a Single protein structure of sequence from Rattus norvegicus. Full crystallographic information is available from OCA.

ReferenceReference

Swapping the substrate specificities of the neuropeptidases neurolysin and thimet oligopeptidase., Lim EJ, Sampath S, Coll-Rodriguez J, Schmidt J, Ray K, Rodgers DW, J Biol Chem. 2007 Mar 30;282(13):9722-32. Epub 2007 Jan 24. PMID:17251185

Structure of neurolysin reveals a deep channel that limits substrate access., Brown CK, Madauss K, Lian W, Beck MR, Tolbert WD, Rodgers DW, Proc Natl Acad Sci U S A. 2001 Mar 13;98(6):3127-32. Epub 2001 Mar 6. PMID:11248043

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Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA

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 {{STRUCTURE_2o3e|  PDB=2o3e  |  SCENE=  }}
-'''Crystal structure of engineered neurolysin with thimet oligopeptidase specificity for neurotensin cleavage site.'''
+===Crystal structure of engineered neurolysin with thimet oligopeptidase specificity for neurotensin cleavage site.===
-==Overview==
+<!--
-Thimet oligopeptidase (EC 3.4.24.15) and neurolysin (EC 3.4.24.16) are closely related zinc-dependent metallopeptidases that metabolize small bioactive peptides. They cleave many substrates at the same sites, but they recognize different positions on others, including neurotensin, a 13-residue peptide involved in modulation of dopaminergic circuits, pain perception, and thermoregulation. On the basis of crystal structures and previous mapping studies, four sites (Glu-469/Arg-470, Met-490/Arg-491, His-495/Asn-496, and Arg-498/Thr-499; thimet oligopeptidase residues listed first) in their substrate-binding channels appear positioned to account for differences in specificity. Thimet oligopeptidase mutated so that neurolysin residues are at all four positions cleaves neurotensin at the neurolysin site, and the reverse mutations in neurolysin switch hydrolysis to the thimet oligopeptidase site. Using a series of constructs mutated at just three of the sites, it was determined that mutations at only two (Glu-469/Arg-470 and Arg-498/Thr-499) are required to swap specificity, a result that was confirmed by testing the two-mutant constructs. If only either one of the two sites is mutated in thimet oligopeptidase, then the enzyme cleaves almost equally at the two hydrolysis positions. Crystal structures of both two-mutant constructs show that the mutations do not perturb local structure, but side chain conformations at the Arg-498/Thr-499 position differ from those of the mimicked enzyme. A model for differential recognition of neurotensin based on differences in surface charge distribution in the substrate binding sites is proposed. The model is supported by the finding that reducing the positive charge on the peptide results in cleavage at both hydrolysis sites.
+The line below this paragraph, {{ABSTRACT_PUBMED_17251185}}, adds the Publication Abstract to the page
+(as it appears on PubMed at http://www.pubmed.gov), where 17251185 is the PubMed ID number.
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+{{ABSTRACT_PUBMED_17251185}}
 ==About this Structure==
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 ==Reference==
 Swapping the substrate specificities of the neuropeptidases neurolysin and thimet oligopeptidase., Lim EJ, Sampath S, Coll-Rodriguez J, Schmidt J, Ray K, Rodgers DW, J Biol Chem. 2007 Mar 30;282(13):9722-32. Epub 2007 Jan 24. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/17251185 17251185]
+Structure of neurolysin reveals a deep channel that limits substrate access., Brown CK, Madauss K, Lian W, Beck MR, Tolbert WD, Rodgers DW, Proc Natl Acad Sci U S A. 2001 Mar 13;98(6):3127-32. Epub 2001 Mar 6. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/11248043 11248043]
 [[Category: Neurolysin]]
 [[Category: Rattus norvegicus]]
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 [[Category: Substrate-binding channel]]
 [[Category: Thermolysin-like domain]]
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+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jul 28 03:17:59 2008''