2ZM4

Crystal structure of imidazo quinoxaline 1 bound to the kinase domain of human LCK, activated form (auto-phosphorylated on TYR394)

Summary for 2ZM4

• Entry DOI: 10.2210/pdb2zm4/pdb
• Related: 2ZM1 3LCK
• Descriptor: Proto-oncogene tyrosine-protein kinase LCK, SULFATE ION, DIMETHYL SULFOXIDE, ... (5 entities in total)
• Functional Keywords: tyrosine-protein kinase, atp-binding, phosphorylation, signal transduction, alternative splicing, chromosomal rearrangement, cytoplasm, disease mutation, host-virus interaction, lipoprotein, membrane, myristate, nucleotide-binding, palmitate, phosphoprotein, proto-oncogene, sh2 domain, sh3 domain, transferase
• Biological source: Homo sapiens (Human)
• Cellular location: Cytoplasm: P06239
• Total number of polymer chains: 1
• Total formula weight: 33742.77

Authors

Tsuji, E. (deposition date: 2008-04-11, release date: 2008-10-14, Last modification date: 2024-10-09)

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

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: 18977146
DOI: 10.1016/j.bmc.2008.10.041

Experimental method

X-RAY DIFFRACTION (2.7 Å)