Origin of asymmetry in adenylyl cyclases: structures of Mycobacterium tuberculosis Rv1900c
| Autor: | Martina Wetterer, Sangita C. Sinha, Jürgen U. Linder, Joachim E. Schultz, Stephen R. Sprang |
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| Rok vydání: | 2005 |
| Předmět: |
Models
Molecular Gs alpha subunit Ribose Molecular Sequence Data Crystallography X-Ray Cyclase Article General Biochemistry Genetics and Molecular Biology Phosphates Substrate Specificity Adenylyl cyclase chemistry.chemical_compound Adenosine Triphosphate Amino Acid Sequence Protein Structure Quaternary Molecular Biology ADCY6 Binding Sites ADCY5 General Immunology and Microbiology biology General Neuroscience ADCY9 Titrimetry Active site Mycobacterium tuberculosis ADCY3 Protein Structure Tertiary Kinetics chemistry Biochemistry Metals biology.protein Dimerization Sequence Alignment Adenylyl Cyclases Protein Binding |
| Zdroj: | The EMBO Journal. 24:663-673 |
| ISSN: | 1460-2075 0261-4189 |
| Popis: | Rv1900c, a Mycobacterium tuberculosis adenylyl cyclase, is composed of an N-terminal alpha/beta-hydrolase domain and a C-terminal cyclase homology domain. It has an unusual 7% guanylyl cyclase side-activity. A canonical substrate-defining lysine and a catalytic asparagine indispensable for mammalian adenylyl cyclase activity correspond to N342 and H402 in Rv1900c. Mutagenic analysis indicates that these residues are dispensable for activity of Rv1900c. Structures of the cyclase homology domain, solved to 2.4 A both with and without an ATP analog, form isologous, but asymmetric homodimers. The noncanonical N342 and H402 do not interact with the substrate. Subunits of the unliganded open dimer move substantially upon binding substrate, forming a closed dimer similar to the mammalian cyclase heterodimers, in which one interfacial active site is occupied and the quasi-dyad-related active site is occluded. This asymmetry indicates that both active sites cannot simultaneously be catalytically active. Such a mechanism of half-of-sites-reactivity suggests that mammalian heterodimeric adenylyl cyclases may have evolved from gene duplication of a primitive prokaryote-type cyclase, followed by loss of function in one active site. |
| Databáze: | OpenAIRE |
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