Jitrapakdee Sarawut, Wallace John C
Department of Biochemistry, Faculty of Science, Mahidol University, Bangkok, Thailand.
Curr Protein Pept Sci. 2003 Jun;4(3):217-29. doi: 10.2174/1389203033487199.
The biotin carboxylase family is comprised of a group of enzymes that utilize a covalently bound prosthetic group, biotin, as a cofactor. These enzymes, which include acetyl-CoA carboxylase, pyruvate carboxylase, propionyl-CoA carboxylase, methylcrotonyl-CoA carboxylase, geranoyl-CoA carboxylase, oxaloacetate decarboxylase, methylmalonyl-CoA decarboxylase, transcarboxylase and urea amidolyase, are found in diverse biosynthetic pathways in both pro-karyotes and eukaryotes. The reactions catalyzed by most members of this group of enzymes share two common features: (1) carboxylation of biotin, apparently via the formation of a carboxyphosphate intermediate, followed by (2) transcarboxylation of CO(2) from biotin to specific acceptor molecules to yield different products. Structural determinations by NMR and X-ray crystallography, complemented by mutagenesis studies, have identified some motifs that are structurally or catalytically important. Analysis of the amino acid sequences of a number of biotin carboxylases not only shows remarkable similarities within certain domains but also that there appears to have been domain rearrangements between groups of carboxylases. Acyl-coenzyme A derivatives, which bind either as substrates or as allosteric regulators of the biotin carboxylases, do not appear to share any of the CoA binding motifs that have been identified in other CoA-SH/acyl-CoA binding proteins. Further comparisons of biotin-dependent carboxylases with other groups of enzymes in the protein data bank reveal that this family of biotin enzymes has strong similarities in specific domains to a number of ATP-utilizing enzymes and to the lipoyl-containing enzymes. These structural homologies are so extensive as to be highly suggestive of evolutionary relationships between biotin carboxylases and these other enzymes.
生物素羧化酶家族由一组利用共价结合的辅基生物素作为辅因子的酶组成。这些酶包括乙酰辅酶A羧化酶、丙酮酸羧化酶、丙酰辅酶A羧化酶、甲基巴豆酰辅酶A羧化酶、香叶酰辅酶A羧化酶、草酰乙酸脱羧酶、甲基丙二酰辅酶A脱羧酶、转羧酶和尿素酰胺酶，存在于原核生物和真核生物的多种生物合成途径中。该组酶的大多数成员催化的反应具有两个共同特征：（1）生物素的羧化，显然是通过形成羧基磷酸中间体，随后是（2）将二氧化碳从生物素转移到特定的受体分子上以产生不同的产物。通过核磁共振和X射线晶体学进行的结构测定，辅以诱变研究，已经确定了一些在结构或催化方面很重要的基序。对多种生物素羧化酶氨基酸序列的分析不仅显示了某些结构域内的显著相似性，而且还表明羧化酶组之间似乎存在结构域重排。酰基辅酶A衍生物，作为生物素羧化酶的底物或变构调节剂结合，似乎不共享在其他辅酶A-SH/酰基辅酶A结合蛋白中已鉴定出的任何辅酶A结合基序。将生物素依赖性羧化酶与蛋白质数据库中的其他酶组进行进一步比较发现，这个生物素酶家族在特定结构域与许多利用ATP的酶和含硫辛酰胺的酶有很强的相似性。这些结构同源性非常广泛，强烈暗示了生物素羧化酶与这些其他酶之间的进化关系。
