Department of Biochemistry and Molecular Biology, The University of Kansas Medical Center, MS 3030, 3901 Rainbow Boulevard, Kansas City, Kansas 66160, United States.
Biochemistry. 2011 Mar 22;50(11):1934-9. doi: 10.1021/bi200052e. Epub 2011 Feb 14.
The binding site for allosteric inhibitor (amino acid) is highly conserved between human liver pyruvate kinase (hL-PYK) and the rabbit muscle isozyme (rM(1)-PYK). To detail similarities/differences in the allosteric function of these two homologues, we quantified the binding of 45 amino acid analogues to hL-PYK and their allosteric impact on affinity for the substrate, phosphoenolpyruvate (PEP). This complements a similar study previously completed for rM(1)-PYK. In hL-PYK, the minimum chemical requirements for effector binding are the same as those identified for rM(1)-PYK (i.e., the l-2-aminopropanaldehyde substructure of the effector is primarily responsible for binding). However, different regions of the effector determine the magnitude of the allosteric response in hL-PYK vs rM(1)-PYK. This finding is inconsistent with the idea that allosteric pathways are conserved between homologues of a protein family.
别构抑制剂（氨基酸）的结合位点在人肝丙酮酸激酶（hL-PYK）和兔肌同工酶（rM(1)-PYK）之间高度保守。为了详细描述这两种同源物的别构功能的相似性/差异性，我们定量测定了 45 种氨基酸类似物与 hL-PYK 的结合及其对底物磷酸烯醇丙酮酸（PEP）亲和力的别构影响。这补充了之前对 rM(1)-PYK 完成的类似研究。在 hL-PYK 中，效应物结合的最小化学要求与为 rM(1)-PYK 确定的要求相同（即，效应物的 l-2-氨基丙醛亚结构主要负责结合）。然而，效应物的不同区域决定了 hL-PYK 与 rM(1)-PYK 之间别构反应的幅度。这一发现与蛋白家族同源物之间的别构途径保守的观点不一致。
