Title data
Steegborn, Clemens ; Litvin, Tatiana N. ; Levin, Lonny R. ; Buck, Jochen ; Wu, Hao:
Bicarbonate activation of adenylyl cyclase via promotion of catalytic active site closure and metal recruitment.
In: Nature Structural & Molecular Biology.
Vol. 12
(January 2005)
Issue 1
.
- pp. 32-37.
ISSN 1545-9985
DOI: https://doi.org/10.1038/nsmb880
Abstract in another language
In an evolutionarily conserved signaling pathway, 'soluble' adenylyl cyclases (sACs) synthesize the ubiquitous second messenger cyclic adenosine 3',5'-monophosphate (cAMP) in response to bicarbonate and calcium signals. Here, we present crystal structures of a cyanobacterial sAC enzyme in complex with ATP analogs, calcium and bicarbonate, which represent distinct catalytic states of the enzyme. The structures reveal that calcium occupies the first ion-binding site and directly mediates nucleotide binding. The single ion-occupied, nucleotide-bound state defines a novel, open adenylyl cyclase state. In contrast, bicarbonate increases the catalytic rate by inducing marked active site closure and recruiting a second, catalytic ion. The phosphates of the bound substrate analogs are rearranged, which would facilitate product formation and release. The mechanisms of calcium and bicarbonate sensing define a reaction pathway involving active site closure and metal recruitment that may be universal for class III cyclases.
Further data
Item Type: | Article in a journal |
---|---|
Refereed: | Yes |
Additional notes: | PubMed-ID: 15689969 |
Institutions of the University: | Faculties > Faculty of Biology, Chemistry and Earth Sciences > Department of Chemistry > Chair Biochemistry > Chair Biochemistry - Univ.-Prof. Dr. Clemens Steegborn Faculties Faculties > Faculty of Biology, Chemistry and Earth Sciences Faculties > Faculty of Biology, Chemistry and Earth Sciences > Department of Chemistry Faculties > Faculty of Biology, Chemistry and Earth Sciences > Department of Chemistry > Chair Biochemistry |
Result of work at the UBT: | No |
DDC Subjects: | 500 Science > 540 Chemistry |
Date Deposited: | 14 Apr 2015 10:11 |
Last Modified: | 14 Apr 2015 10:11 |
URI: | https://eref.uni-bayreuth.de/id/eprint/10136 |