2ZYB
Crystal structure of phenylimidazo pyrazin 2 bound to the kinase domain of human LCK, (auto-phosphorylated on TYR394)
Summary for 2ZYB
| Entry DOI | 10.2210/pdb2zyb/pdb |
| Related | 2ZOB 3LCK |
| Descriptor | Proto-oncogene tyrosine-protein kinase LCK, SULFATE ION, N-(2,6-dimethylphenyl)-5-phenylimidazo[1,5-a]pyrazin-8-amine, ... (4 entities in total) |
| Functional Keywords | tyrosine-protein kinase, atp-binding, phosphorylation, signal transduction, alternative splicing, chromosomal rearrangement, cytoplasm, disease mutation, host-virus interaction, kinase, lipoprotein, membrane, myristate, nucleotide-binding, palmitate, phosphoprotein, proto-oncogene, sh2 domain, sh3 domain, transferase, cell membrane, polymorphism |
| Biological source | Homo sapiens (Human) |
| Cellular location | Cytoplasm: P06239 |
| Total number of polymer chains | 1 |
| Total formula weight | 33476.05 |
| Authors | Tsuji, E. (deposition date: 2009-01-19, release date: 2009-02-03, Last modification date: 2024-11-20) |
| Primary citation | Ozawa, T.,Tsuji, E.,Ozawa, M.,Handa, C.,Mukaiyama, H.,Nishimura, T.,Kobayashi, S.,Okazaki, K. The importance of CH/pi hydrogen bonds in rational drug design: An ab initio fragment molecular orbital study to leukocyte-specific protein tyrosine (LCK) kinase Bioorg.Med.Chem., 16:10311-10318, 2008 Cited by PubMed Abstract: The interaction energy was calculated, by the ab initio FMO method, for complexes between LCK protein and four inhibitors (staurosporine, BMS compound 2, and our compounds 3 and 4). In every case a number of CH/pi hydrogen bonds have been disclosed in the so-called adenine pocket. In complexes of 2, 3, and 4, CH/pi and NH/pi hydrogen bonds have been observed in another pocket. In view of the above results, the aniline ring of 3 was replaced by 2,6-dimethyl aniline to increase the potency for LCK kinase. A 10-fold increase in the potency has been achieved for 4 over 3. We suggest that the concept of weak hydrogen bonds is useful in the rational design of drugs. PubMed: 18977146DOI: 10.1016/j.bmc.2008.10.041 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.55 Å) |
Structure validation
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