A molecular switch and proton wire synchronize the active sites in thiamine enzymes

被引：154

作者：

Frank, RAW ^{[1
]}

Titman, CM ^{[1
]}

Pratap, JV ^{[1
]}

Luisi, BF ^{[1
]}

Perham, RN ^{[1
]}

机构：

[1] Univ Cambridge, Dept Biochem, Cambridge CB2 1QW, England

来源：

SCIENCE | 2004年 / 306卷 / 5697期

关键词：

D O I：

10.1126/science.1101030

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Thiamine diphosphate (ThDP) is used as a cofactor in many key metabolic enzymes. We present evidence that the ThDPs in the two active sites of the E1 (EC 1.2.4.1) component of the pyruvate dehydrogenase complex communicate over a distance of 20 angstroms by reversibly shuttling a proton through an acidic tunnel in the protein. This "proton wire" permits the cofactors to serve reciprocally as general acid/base in catalysis and to switch the conformation of crucial active-site peptide loops. This synchronizes the progression of chemical events and can account for the oligomeric organization, conformational asymmetry, and "ping-pong" kinetic properties of E1 and other thiamine-dependent enzymes.

引用

页码：872 / 876

页数：5

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