| pubmed-article:16539372 | rdf:type | pubmed:Citation | lld:pubmed |
| pubmed-article:16539372 | lifeskim:mentions | umls-concept:C0332307 | lld:lifeskim |
| pubmed-article:16539372 | lifeskim:mentions | umls-concept:C0031640 | lld:lifeskim |
| pubmed-article:16539372 | lifeskim:mentions | umls-concept:C0444626 | lld:lifeskim |
| pubmed-article:16539372 | lifeskim:mentions | umls-concept:C0012632 | lld:lifeskim |
| pubmed-article:16539372 | lifeskim:mentions | umls-concept:C1719039 | lld:lifeskim |
| pubmed-article:16539372 | lifeskim:mentions | umls-concept:C0599473 | lld:lifeskim |
| pubmed-article:16539372 | pubmed:issue | 6 | lld:pubmed |
| pubmed-article:16539372 | pubmed:dateCreated | 2006-3-16 | lld:pubmed |
| pubmed-article:16539372 | pubmed:databankReference | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:16539372 | pubmed:databankReference | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:16539372 | pubmed:abstractText | Type 4 phosphodiesterase (PDE4) inhibitors are emerging as new treatments for a number of disorders including asthma and chronic obstructive pulmonary disease. Here we report the biochemical characterization on the second generation inhibitor (+)-1 (L-, IC50=0.4 nM) and its enantiomer (-)-1 (L-, IC50=43 nM) and their cocrystal structures with PDE4D at 2.0 A resolution. Despite the 107-fold affinity difference, both enantiomers interact with the same sets of residues in the rigid active site. The weaker (-)-1 adopts an unfavorable conformation to preserve the pivotal interactions between the Mg-bound waters and the N-oxide of pyridine. These structures support a model in which inhibitors are anchored by the invariant glutamine at one end and the metal-pocket residues at another end. This model provides explanations for most of the observed structure-activity relationship and the metal ion dependency of the catechol-ether based inhibitors and should facilitate their further design. | lld:pubmed |
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| pubmed-article:16539372 | pubmed:language | eng | lld:pubmed |
| pubmed-article:16539372 | pubmed:journal | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:16539372 | pubmed:citationSubset | IM | lld:pubmed |
| pubmed-article:16539372 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:16539372 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
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| pubmed-article:16539372 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:16539372 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:16539372 | pubmed:status | MEDLINE | lld:pubmed |
| pubmed-article:16539372 | pubmed:month | Mar | lld:pubmed |
| pubmed-article:16539372 | pubmed:issn | 0022-2623 | lld:pubmed |
| pubmed-article:16539372 | pubmed:author | pubmed-author:KeHengmingH | lld:pubmed |
| pubmed-article:16539372 | pubmed:author | pubmed-author:HuangZhengZ | lld:pubmed |
| pubmed-article:16539372 | pubmed:author | pubmed-author:RobinsonHowar... | lld:pubmed |
| pubmed-article:16539372 | pubmed:author | pubmed-author:HuaiQingQ | lld:pubmed |
| pubmed-article:16539372 | pubmed:author | pubmed-author:WangHuanchenH | lld:pubmed |
| pubmed-article:16539372 | pubmed:author | pubmed-author:SunYingjieY | lld:pubmed |
| pubmed-article:16539372 | pubmed:author | pubmed-author:AspiotisRenée... | lld:pubmed |
| pubmed-article:16539372 | pubmed:author | pubmed-author:MacdonaldDwig... | lld:pubmed |
| pubmed-article:16539372 | pubmed:issnType | Print | lld:pubmed |
| pubmed-article:16539372 | pubmed:day | 23 | lld:pubmed |
| pubmed-article:16539372 | pubmed:volume | 49 | lld:pubmed |
| pubmed-article:16539372 | pubmed:owner | NLM | lld:pubmed |
| pubmed-article:16539372 | pubmed:authorsComplete | Y | lld:pubmed |
| pubmed-article:16539372 | pubmed:pagination | 1867-73 | lld:pubmed |
| pubmed-article:16539372 | pubmed:dateRevised | 2009-11-18 | lld:pubmed |
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| pubmed-article:16539372 | pubmed:meshHeading | pubmed-meshheading:16539372... | lld:pubmed |
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| pubmed-article:16539372 | pubmed:meshHeading | pubmed-meshheading:16539372... | lld:pubmed |
| pubmed-article:16539372 | pubmed:meshHeading | pubmed-meshheading:16539372... | lld:pubmed |
| pubmed-article:16539372 | pubmed:meshHeading | pubmed-meshheading:16539372... | lld:pubmed |
| pubmed-article:16539372 | pubmed:year | 2006 | lld:pubmed |
| pubmed-article:16539372 | pubmed:articleTitle | Enantiomer discrimination illustrated by the high resolution crystal structures of type 4 phosphodiesterase. | lld:pubmed |
| pubmed-article:16539372 | pubmed:affiliation | Department of Biochemistry and Biophysics and Lineberger Comprehensive Cancer Center, The University of North Carolina, Chapel Hill, North Carolina 27599-7260, USA. | lld:pubmed |
| pubmed-article:16539372 | pubmed:publicationType | Journal Article | lld:pubmed |
| pubmed-article:16539372 | pubmed:publicationType | Research Support, N.I.H., Extramural | lld:pubmed |
| http://linkedlifedata.com/r... | http://linkedlifedata.com/r... | pubmed-article:16539372 | lld:chembl |
| http://linkedlifedata.com/r... | pubmed:referesTo | pubmed-article:16539372 | lld:pubmed |
