Crystal Structure of Methanobacterium thermoautotrophicum Phosphoribosyl-AMP Cyclohydrolase HisI

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• 作者：J. Sivaraman ; Rebecca S. Myers ; Lorena Boju ; Traian Sulea ; Miroslaw Cygler ; V. Jo Davisson ; and Joseph D. Schrag
• 刊名：Biochemistry
• 出版年：2005
• 出版时间：August 2, 2005
• 年：2005
• 卷：44
• 期：30
• 页码：10071 - 10080
• 全文大小：512K
• 年卷期：v.44,no.30(August 2, 2005)
• ISSN：1520-4995

文摘

The metabolic pathway for histidine biosynthesis is interesting from an evolutionary perspectivebecause of the diversity of gene organizations and protein structures involved. Hydrolysis of phosphoribosyl-AMP, the third step in the histidine biosynthetic pathway, is carried out by PR-AMP cyclohydrolase, theproduct of the hisI gene. The three-dimensional structure of PR-AMP cyclohydrolase from Methanobacterium thermoautotrophicum was solved and refined to 1.7 Å resolution. The enzyme is a homodimer.The position of the Zn²⁺-binding site that is essential for catalysis was inferred from the positions ofbound Cd²⁺ ions, which were part of the crystallization medium. These metal binding sites include threecysteine ligands, two from one monomer and the third from the second monomer. The enzyme remainsactive when Cd²⁺ is substituted for Zn²⁺. The likely binding site for Mg²⁺, also necessary for activity ina homologous cyclohydrolase, was also inferred from Cd²⁺ positions and is comprised of aspartic acidside chains. The putative substrate-binding cleft is formed at the interface between the two monomers ofthe dimer. This fact, combined with the localization of the Zn²⁺-binding site, indicates that the enzymeis an obligate dimer.