Molecular Dynamics Simulations of Biotin Carboxylase
详细信息 查看全文
- 作者：Sten O. Nilsson Lill ; Jiali Gao ; Grover L. Waldrop
- 刊名：Journal of Physical Chemistry B
- 出版年：2008
- 出版时间：March 13, 2008
- 年：2008
- 卷：112
- 期：10
- 页码：3149 - 3156
- 全文大小：502K
- 年卷期：v.112,no.10(March 13, 2008)
- ISSN：1520-5207
文摘
Biotin carboxylase catalyzes the ATP-dependent carboxylation of biotin and is one component of themultienzyme complex acetyl-CoA carboxylase that catalyzes the first committed step in fatty acid synthesisin all organisms. Biotin carboxylase from Escherichia coli, whose crystal structures with and without ATPbound have been determined, has served as a model system for this component of the acetyl-CoA carboxylasecomplex. The two crystal structures revealed a large conformational change of one domain relative to theother domains when ATP is bound. Unfortunately, the crystal structure with ATP bound was obtained withan inactive site-directed mutant of the enzyme. As a consequence the structure with ATP bound lacked keystructural information such as for the Mg2+ ions and contained altered conformations of key active-site residues.Therefore, nanosecond molecular dynamics studies of the wild-type biotin carboxylase were undertaken tosupplant and amend the results of the crystal structures. Specifically, the protein-metal interactions of thetwo catalytically critical Mg2+ ions bound in the active site are presented along with a reevaluation of theconformations of active-site residues bound to ATP. In addition, the regions of the polypeptide chain thatserve as hinges for the large conformational change were identified. The results of the hinge analysiscomplemented a covariance analysis that identified the individual structural elements of biotin carboxylasethat change their conformation in response to ATP binding.