Source:http://linkedlifedata.com/resource/pubmed/id/16183633
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
48
|
| pubmed:dateCreated |
2005-11-28
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| pubmed:databankReference | |
| pubmed:abstractText |
Reversible modification of Atg8 with phosphatidylethanolamine is crucial for autophagy, the bulk degradation system conserved in eukaryotic cells. Atg4 is a novel cysteine protease that processes and deconjugates Atg8. Herein, we report the crystal structure of human Atg4B (HsAtg4B) at 1.9-A resolution. Despite no obvious sequence homology with known proteases, the structure of HsAtg4B shows a classical papain-like fold. In addition to the papain fold region, HsAtg4B has a small alpha/beta-fold domain. This domain is thought to be the binding site for Atg8 homologs. The active site cleft of HsAtg4B is masked by a loop (residues 259-262), implying a conformational change upon substrate binding. The structure and in vitro mutational analyses provide the basis for the specificity and catalysis of HsAtg4B. This will enable the design of Atg4-specific inhibitors that block autophagy.
|
| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical | |
| pubmed:status |
MEDLINE
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| pubmed:month |
Dec
|
| pubmed:issn |
0021-9258
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| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:day |
2
|
| pubmed:volume |
280
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
40058-65
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| pubmed:dateRevised |
2006-11-15
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| pubmed:meshHeading |
pubmed-meshheading:16183633-Amino Acid Sequence,
pubmed-meshheading:16183633-Autophagy,
pubmed-meshheading:16183633-Binding Sites,
pubmed-meshheading:16183633-Catalysis,
pubmed-meshheading:16183633-Catalytic Domain,
pubmed-meshheading:16183633-Crystallography, X-Ray,
pubmed-meshheading:16183633-Cysteine Endopeptidases,
pubmed-meshheading:16183633-Electrophoresis, Polyacrylamide Gel,
pubmed-meshheading:16183633-Glutathione Transferase,
pubmed-meshheading:16183633-Humans,
pubmed-meshheading:16183633-Models, Molecular,
pubmed-meshheading:16183633-Molecular Sequence Data,
pubmed-meshheading:16183633-Mutagenesis,
pubmed-meshheading:16183633-Mutation,
pubmed-meshheading:16183633-Papain,
pubmed-meshheading:16183633-Protein Binding,
pubmed-meshheading:16183633-Protein Conformation,
pubmed-meshheading:16183633-Protein Folding,
pubmed-meshheading:16183633-Substrate Specificity
|
| pubmed:year |
2005
|
| pubmed:articleTitle |
Structural basis for the specificity and catalysis of human Atg4B responsible for mammalian autophagy.
|
| pubmed:affiliation |
Department of Structural Biology, Graduate School of Pharmaceutical Sciences, Hokkaido University, N-12, W-6, Kita-ku, Sapporo 060-0812, Japan.
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| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
|