Coenzyme B12 (cobalamin)-dependent enzymes.
Coenzyme B12 (cobalamin)-dependent enzymes.
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DOI：
10.1042/bse0340139
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发表时间：
1999-11
影响因子：
6.4
通讯作者：
E. Marsh
中科院分区：
文献类型：
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作者：
E. Marsh
B12或钴胺素辅酶是复杂的大环化合物，其反应性与独特的钴-碳键有关。两种生物活性形式是MeCbl和MeCbl及其密切相关的钴酰胺形式。MeCbl作为活化甲基的中间载体参与。在催化循环中，辅酶在MeCbl和高度亲核的cob（I）alamin形式之间穿梭。MeCbll依赖性酶的例子包括甲硫氨酸合成酶和Me-H4-MPT：辅酶M甲基转移酶。辅酶Cbl作为碳基自由基的来源，其通过辅酶的钴-碳键的均裂而暴露。自由基随后用于从基材上除去非酸性氢原子，以促进涉及碳-碳、碳-氧和碳-氮键断裂的各种反应。大多数反应涉及羟基、氨基和含碳基团的1，2迁移，但也有一类核糖核苷酸还原酶使用C1, 2Cbl。两个钴胺素依赖酶，蛋氨酸合成酶和甲基丙二酰辅酶A的结构已经解决。在这两种情况下，钴都与来自蛋白质的组氨酸配体配位。这种结合基序的意义目前尚不清楚，因为在其他钴胺素依赖性酶中，光谱证据表明辅酶的核苷酸“尾巴”在与蛋白质结合时仍然与钴配位。
The B12 or cobalamin coenzymes are complex macrocycles whose reactivity is associated with a unique cobalt-carbon bond. The two biologically active forms are MeCbl and AdoCbl and their closely related cobamide forms. MeCbl participates as the intermediate carrier of activated methyl groups. During the catalytic cycle the coenzyme shuttles between MeCbl and the highly nucleophilic cob(I)alamin form. Examples of MeCbl-dependent enzymes include methionine synthase and Me-H4-MPT: coenzyme M methyl transferase. AdoCbl functions as a source of carbon-based free radicals that are unmasked by homolysis of the coenzyme's cobalt-carbon bond. The free radicals are subsequently used to remove non-acid hydrogen atoms from substrates to facilitate a variety of reactions involving cleavage of carbon-carbon, carbon-oxygen and carbon-nitrogen bonds. Most reactions involve 1,2 migrations of hydroxy-, amino- and carbon-containing groups, but there is also one class of ribonucleotide reductases that uses AdoCbl. The structures of two cobalamin-dependent enzymes, methionine synthase and methylmalonyl-CoA mutase, have been solved. In both cases the cobalt is co-ordinated by a histidine ligand from the protein. The significance of this binding motif is presently unclear since in other cobalamin-dependent enzymes spectroscopic evidence suggests that the coenzyme's nucleotide 'tail' remains co-ordinated to cobalt when bound to the protein.