1yk9: Difference between revisions

Revision as of 17:06, 21 February 2008

Crystal structure of a mutant form of the mycobacterial adenylyl cyclase Rv1625c

OverviewOverview

The Rv1625c Class III adenylyl cyclase from Mycobacterium tuberculosis is a homodimeric enzyme with two catalytic centers at the dimer interface, and shows sequence similarity with the mammalian adenylyl and guanylyl cyclases. Mutation of the substrate-specifying residues in the catalytic domain of Rv1625c, either independently or together, to those present in guanylyl cyclases not only failed to confer guanylyl cyclase activity to the protein, but also severely abrogated the adenylyl cyclase activity of the enzyme. Biochemical analysis revealed alterations in the behavior of the mutants on ion-exchange chromatography, indicating differences in the surface-exposed charge upon mutation of substrate-specifying residues. The mutant proteins showed alterations in oligomeric status as compared to the wild-type enzyme, and differing abilities to heterodimerize with the wild-type protein. The crystal structure of a mutant has been solved to a resolution of 2.7A. On the basis of the structure, and additional biochemical studies, we provide possible reasons for the altered properties of the mutant proteins, as well as highlight unique structural features of the Rv1625c adenylyl cyclase.

About this StructureAbout this Structure

1YK9 is a Single protein structure of sequence from Mycobacterium tuberculosis. Active as Adenylate cyclase, with EC number 4.6.1.1 Full crystallographic information is available from OCA.

ReferenceReference

A structural basis for the role of nucleotide specifying residues in regulating the oligomerization of the Rv1625c adenylyl cyclase from M. tuberculosis., Ketkar AD, Shenoy AR, Ramagopal UA, Visweswariah SS, Suguna K, J Mol Biol. 2006 Mar 3;356(4):904-16. Epub 2005 Dec 22. PMID:16403515

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OCA

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-[[Image:1yk9.gif|left|200px]]<br /><applet load="1yk9" size="450" color="white" frame="true" align="right" spinBox="true"
+[[Image:1yk9.gif|left|200px]]<br /><applet load="1yk9" size="350" color="white" frame="true" align="right" spinBox="true"
 caption="1yk9, resolution 2.70&Aring;" />
 '''Crystal structure of a mutant form of the mycobacterial adenylyl cyclase Rv1625c'''<br />
 ==Overview==
-The Rv1625c Class III adenylyl cyclase from Mycobacterium tuberculosis is, a homodimeric enzyme with two catalytic centers at the dimer interface, and shows sequence similarity with the mammalian adenylyl and guanylyl, cyclases. Mutation of the substrate-specifying residues in the catalytic, domain of Rv1625c, either independently or together, to those present in, guanylyl cyclases not only failed to confer guanylyl cyclase activity to, the protein, but also severely abrogated the adenylyl cyclase activity of, the enzyme. Biochemical analysis revealed alterations in the behavior of, the mutants on ion-exchange chromatography, indicating differences in the, surface-exposed charge upon mutation of substrate-specifying residues. The, mutant proteins showed alterations in oligomeric status as compared to the, wild-type enzyme, and differing abilities to heterodimerize with the, wild-type protein. The crystal structure of a mutant has been solved to a, resolution of 2.7A. On the basis of the structure, and additional, biochemical studies, we provide possible reasons for the altered, properties of the mutant proteins, as well as highlight unique structural, features of the Rv1625c adenylyl cyclase.
+The Rv1625c Class III adenylyl cyclase from Mycobacterium tuberculosis is a homodimeric enzyme with two catalytic centers at the dimer interface, and shows sequence similarity with the mammalian adenylyl and guanylyl cyclases. Mutation of the substrate-specifying residues in the catalytic domain of Rv1625c, either independently or together, to those present in guanylyl cyclases not only failed to confer guanylyl cyclase activity to the protein, but also severely abrogated the adenylyl cyclase activity of the enzyme. Biochemical analysis revealed alterations in the behavior of the mutants on ion-exchange chromatography, indicating differences in the surface-exposed charge upon mutation of substrate-specifying residues. The mutant proteins showed alterations in oligomeric status as compared to the wild-type enzyme, and differing abilities to heterodimerize with the wild-type protein. The crystal structure of a mutant has been solved to a resolution of 2.7A. On the basis of the structure, and additional biochemical studies, we provide possible reasons for the altered properties of the mutant proteins, as well as highlight unique structural features of the Rv1625c adenylyl cyclase.
 ==About this Structure==
-YK9 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Mycobacterium_tuberculosis Mycobacterium tuberculosis]. Active as [http://en.wikipedia.org/wiki/Adenylate_cyclase Adenylate cyclase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=4.6.1.1 4.6.1.1] Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1YK9 OCA].
+YK9 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Mycobacterium_tuberculosis Mycobacterium tuberculosis]. Active as [http://en.wikipedia.org/wiki/Adenylate_cyclase Adenylate cyclase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=4.6.1.1 4.6.1.1] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1YK9 OCA].
 ==Reference==
@@ Line 14: / Line 14: @@
 [[Category: Mycobacterium tuberculosis]]
 [[Category: Single protein]]
-[[Category: Ketkar, A.D.]]
+[[Category: Ketkar, A D.]]
-[[Category: Ramagopal, U.A.]]
+[[Category: Ramagopal, U A.]]
-[[Category: Shenoy, A.R.]]
+[[Category: Shenoy, A R.]]
 [[Category: Suguna, K.]]
-[[Category: TBSGC, TB.Structural.Genomics.Consortium.]]
+[[Category: TBSGC, TB Structural Genomics Consortium.]]
-[[Category: Visweswariah, S.S.]]
+[[Category: Visweswariah, S S.]]
 [[Category: beta-alpha-beta sandwich]]
 [[Category: protein structure initiative]]
@@ Line 27: / Line 27: @@
 [[Category: tbsgc]]
-''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Wed Nov 21 06:51:27 2007''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:06:14 2008''