Fukazawa H, Mizuno S, Uehara Y
Department of Antibiotics, National Institute of Health, Tokyo, Japan.
Biochem Biophys Res Commun. 1990 Nov 30;173(1):276-82. doi: 10.1016/s0006-291x(05)81053-8.
Herbimycin A is an antiobiotic which reverses transformation caused by src family oncogenes. It inactivates p60v-src in vitro, possibly by binding to reactive SH-group(s) of the kinase. We examined effects of various SH-reagents on p60v-src and observed that N-[p-(2-benzimidazolyl)phenyl]maleimide (BIPM) or N-(9-acridinyl)maleimide (NAM) were potent inactivators of the kinase, whereas N-ethylmaleimide (NEM) required high concentrations, and iodoacetamide was totally ineffective in reducing the kinase activity. Pretreatment of p60v-src immune-complex with NEM and iodoacetamide, however, protected the kinase from inactivation by herbimycin A, BIPM, and NAM. The results suggest that SH-group(s) to which herbimycin A binds is not essential for the kinase activity, but is positioned in the vicinity of the active center.
除莠霉素A是一种抗生素，可逆转由src家族癌基因引起的转化。它在体外使p60v-src失活，可能是通过与激酶的反应性巯基结合。我们研究了各种巯基试剂对p60v-src的影响，发现N-[对-(2-苯并咪唑基)苯基]马来酰亚胺（BIPM）或N-(9-吖啶基)马来酰亚胺（NAM）是该激酶的有效失活剂，而N-乙基马来酰亚胺（NEM）需要高浓度才能起作用，并且碘乙酰胺在降低激酶活性方面完全无效。然而，用NEM和碘乙酰胺对p60v-src免疫复合物进行预处理可保护该激酶不被除莠霉素A、BIPM和NAM失活。结果表明，除莠霉素A结合的巯基对于激酶活性不是必需的，但位于活性中心附近。
