Source:http://linkedlifedata.com/resource/pubmed/id/15697204
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
6
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| pubmed:dateCreated |
2005-2-8
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| pubmed:abstractText |
Missense mutations in the collagen triple-helix that replace one of the required Gly residues in the (Gly-Xaa-Yaa)(n)() repeating sequence have been implicated in various disorders. Although most hereditary collagen disorders are rare, a common occurrence of a Gly replacement mutation is found in the collagenous domain of mannose binding lectin (MBL). A Gly --> Asp mutation at position 54 in MBL is found at a frequency as high as 30% in certain populations and leads to increased susceptibility to infections. The structural and energetic consequences of this mutation are investigated by comparing a triple-helical peptide containing the N-terminal Gly-X-Y units of MBL with the homologous peptide containing the Gly to Asp replacement. The mutation leads to a loss of triple-helix content but only a small decrease in the stability of the triple-helix (DeltaT(m) approximately 2 degrees C) and no change in the calorimetric enthalpy. NMR studies on specifically labeled residues indicate the portion of the peptide C-terminal to residue 54 is in a highly ordered triple-helix in both peptides, while residues N-terminal to the mutation site have a weak triple-helical signal in the parent peptide and are completely disordered in the mutant peptide. These results suggest that the N-terminal triplet residues are contributing little to the stability of this peptide, a hypothesis confirmed by the stability and enthalpy of shorter peptides containing only the region C-terminal to the mutation site. The Gly to Asp replacement at position 54 in MBL occurs at the boundary of a highly stable triple-helix region and a very unstable sequence. The junctional position of this mutation minimizes its destabilizing effect, in contrast with the significant destabilization seen for Gly replacements in peptides modeling collagen diseases.
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| pubmed:grant | |
| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical | |
| pubmed:status |
MEDLINE
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| pubmed:month |
Feb
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| pubmed:issn |
0006-2960
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| pubmed:author | |
| pubmed:issnType |
Print
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| pubmed:day |
15
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| pubmed:volume |
44
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
1793-9
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| pubmed:dateRevised |
2007-11-14
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| pubmed:meshHeading |
pubmed-meshheading:15697204-Amino Acid Sequence,
pubmed-meshheading:15697204-Amino Acid Substitution,
pubmed-meshheading:15697204-Calorimetry, Differential Scanning,
pubmed-meshheading:15697204-Circular Dichroism,
pubmed-meshheading:15697204-Collagen,
pubmed-meshheading:15697204-Humans,
pubmed-meshheading:15697204-Hydrogen Bonding,
pubmed-meshheading:15697204-Mannose-Binding Lectin,
pubmed-meshheading:15697204-Models, Molecular,
pubmed-meshheading:15697204-Molecular Sequence Data,
pubmed-meshheading:15697204-Mutation, Missense,
pubmed-meshheading:15697204-Nuclear Magnetic Resonance, Biomolecular,
pubmed-meshheading:15697204-Peptide Fragments,
pubmed-meshheading:15697204-Protein Conformation,
pubmed-meshheading:15697204-Protein Structure, Tertiary,
pubmed-meshheading:15697204-Thermodynamics
|
| pubmed:year |
2005
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| pubmed:articleTitle |
Stability junction at a common mutation site in the collagenous domain of the mannose binding lectin.
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| pubmed:affiliation |
Department of Biochemistry, UMDNJ-Robert Wood Johnson Medical School, Piscataway, New Jersey 08854, USA.
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| pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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