Abstract
Kinases play central roles in signaling pathways and are promising therapeutic targets for many diseases. Designing selective kinase inhibitors is an emergent and challenging task, because kinases share an evolutionary conserved ATP-binding site. KIDFamMap (http://gemdock.life.nctu. edu.tw/KIDFamMap/) is the first database to explore kinase-inhibitor families (KIFs) and kinase-inhibitor-disease (KID) relationships for kinase inhibitor selectivity and mechanisms. This database includes 1208 KIFs, 962 KIDs, 55603 kinase-inhibitor interactions (KIIs), 35 788 kinase inhibitors, 399 human protein kinases, 339 diseases and 638 disease allelic variants. Here, a KIF can be defined as follows: (i) the kinases in the KIF with significant sequence similarity, (ii) the inhibitors in the KIF with significant topology similarity and (iii) the KIIs in the KIF with significant interaction similarity. The KIIs within a KIF are often conserved on some consensus KIDFamMap anchors, which represent conserved interactions between the kinase subsites and consensus moieties of their inhibitors. Our experimental results reveal that the members of a KIF often possess similar inhibition profiles. The KIDFamMap anchors can reflect kinase conformations types, kinase functions and kinase inhibitor selectivity. We believe that KIDFamMap provides biological insights into kinase inhibitor selectivity and binding mechanisms.
| Original language | English |
|---|---|
| Journal | Nucleic Acids Research |
| Volume | 41 |
| Issue number | D1 |
| DOIs | |
| Publication status | Published - Jan 1 2013 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Genetics
Cite this
KIDFamMap : A database of kinase-inhibitor-disease family maps for kinase inhibitor selectivity and binding mechanisms. / Chiu, Yi Yuan; Lin, Chih Ta; Huang, Jhang Wei; Hsu, Kai Cheng; Tseng, Jen Hu; You, Syuan Ren; Yang, Jinn Moon.
In: Nucleic Acids Research, Vol. 41, No. D1, 01.01.2013.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - KIDFamMap
T2 - A database of kinase-inhibitor-disease family maps for kinase inhibitor selectivity and binding mechanisms
AU - Chiu, Yi Yuan
AU - Lin, Chih Ta
AU - Huang, Jhang Wei
AU - Hsu, Kai Cheng
AU - Tseng, Jen Hu
AU - You, Syuan Ren
AU - Yang, Jinn Moon
PY - 2013/1/1
Y1 - 2013/1/1
N2 - Kinases play central roles in signaling pathways and are promising therapeutic targets for many diseases. Designing selective kinase inhibitors is an emergent and challenging task, because kinases share an evolutionary conserved ATP-binding site. KIDFamMap (http://gemdock.life.nctu. edu.tw/KIDFamMap/) is the first database to explore kinase-inhibitor families (KIFs) and kinase-inhibitor-disease (KID) relationships for kinase inhibitor selectivity and mechanisms. This database includes 1208 KIFs, 962 KIDs, 55603 kinase-inhibitor interactions (KIIs), 35 788 kinase inhibitors, 399 human protein kinases, 339 diseases and 638 disease allelic variants. Here, a KIF can be defined as follows: (i) the kinases in the KIF with significant sequence similarity, (ii) the inhibitors in the KIF with significant topology similarity and (iii) the KIIs in the KIF with significant interaction similarity. The KIIs within a KIF are often conserved on some consensus KIDFamMap anchors, which represent conserved interactions between the kinase subsites and consensus moieties of their inhibitors. Our experimental results reveal that the members of a KIF often possess similar inhibition profiles. The KIDFamMap anchors can reflect kinase conformations types, kinase functions and kinase inhibitor selectivity. We believe that KIDFamMap provides biological insights into kinase inhibitor selectivity and binding mechanisms.
AB - Kinases play central roles in signaling pathways and are promising therapeutic targets for many diseases. Designing selective kinase inhibitors is an emergent and challenging task, because kinases share an evolutionary conserved ATP-binding site. KIDFamMap (http://gemdock.life.nctu. edu.tw/KIDFamMap/) is the first database to explore kinase-inhibitor families (KIFs) and kinase-inhibitor-disease (KID) relationships for kinase inhibitor selectivity and mechanisms. This database includes 1208 KIFs, 962 KIDs, 55603 kinase-inhibitor interactions (KIIs), 35 788 kinase inhibitors, 399 human protein kinases, 339 diseases and 638 disease allelic variants. Here, a KIF can be defined as follows: (i) the kinases in the KIF with significant sequence similarity, (ii) the inhibitors in the KIF with significant topology similarity and (iii) the KIIs in the KIF with significant interaction similarity. The KIIs within a KIF are often conserved on some consensus KIDFamMap anchors, which represent conserved interactions between the kinase subsites and consensus moieties of their inhibitors. Our experimental results reveal that the members of a KIF often possess similar inhibition profiles. The KIDFamMap anchors can reflect kinase conformations types, kinase functions and kinase inhibitor selectivity. We believe that KIDFamMap provides biological insights into kinase inhibitor selectivity and binding mechanisms.
UR - http://www.scopus.com/inward/record.url?scp=84876517808&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84876517808&partnerID=8YFLogxK
U2 - 10.1093/nar/gks1218
DO - 10.1093/nar/gks1218
M3 - Article
C2 - 23193279
AN - SCOPUS:84876517808
VL - 41
JO - Nucleic Acids Research
JF - Nucleic Acids Research
SN - 0305-1048
IS - D1
ER -