PDBsum entry: 1y11

Lyase

PDB id: 1y11

Contents

Protein chain

364 a.a. *

Ligands

SO4

1PE

GOL

* Residue conservation analysis

PDB id:

1y11

Name:

Lyase

Title:

Mycobacterial adenylyl cyclase rv1264, holoenzyme, active st

Structure:

Hypothetical protein rv1264/mt1302. Chain: a. Synonym: adenylyl cyclase. Engineered: yes

Source:

Mycobacterium tuberculosis. Organism_taxid: 1773. Gene: rv1264. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.

Biol. unit:

Dimer (from PDB file)

Resolution:

3.30Å R-factor: 0.238 R-free: 0.299

Authors:

I.Tews,F.Findeisen,I.Sinning,A.Schultz,J.E.Schultz,J.U.Linde

Key ref:

I.Tews et al. (2005). The structure of a pH-sensing mycobacterial adenylyl cyclase holoenzyme. Science, 308, 1020-1023. PubMed id: 15890882 DOI: 10.1126/science.1107642

Date:

16-Nov-04 Release date: 24-May-05

Protein chain

Q11055  (Y1264_MYCTU) -  pH-sensitive adenylate cyclase Rv1264

Seq: 397 a.a.

Struc: 364 a.a.

Enzyme reactions

• Enzyme class: E.C.4.6.1.1 - Adenylate cyclase.
• Reaction: ATP = 3',5'-cyclic AMP + diphosphate
• Cofactor: Pyridoxal 5'-phosphate

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

 Gene Ontology (GO) functional annotation 

• Cellular component: intracellular (1 term)
• Biological process: intracellular signal transduction (6 terms)
• Biochemical function: nucleotide binding (9 terms)

reference

DOI no: 10.1126/science.1107642

Science 308:1020-1023 (2005)

PubMed id: 15890882

The structure of a pH-sensing mycobacterial adenylyl cyclase holoenzyme.

I.Tews, F.Findeisen, I.Sinning, A.Schultz, J.E.Schultz, J.U.Linder.

ABSTRACT

Class III adenylyl cyclases contain catalytic and regulatory domains, yet structural insight into their interactions is missing. We show that the mycobacterial adenylyl cyclase Rv1264 is rendered a pH sensor by its N-terminal domain. In the structure of the inhibited state, catalytic and regulatory domains share a large interface involving catalytic residues. In the structure of the active state, the two catalytic domains rotate by 55 degrees to form two catalytic sites at their interface. Two alpha helices serve as molecular switches. Mutagenesis is consistent with a regulatory role of the structural transition, and we suggest that the transition is regulated by pH.

Selected figure(s)

Figure 2.
Fig. 2. Overall structure of Rv1264 in the active and inhibited states. (A) The active dimer, green, and (B) the inhibited dimer, blue. Monomers are distinguished by dark and light colors. The regulatory domains remain essentially unchanged upon enzyme activation, but the interface with the catalytic domains differs substantially. Secondary structure elements are labeled in the ribbon diagrams (for one monomer); C- and N termini are also indicated. Structural switch regions, red, are found in the linker region and in the catalytic dimer. The boxed regions are shown in detail in Fig. 4. Ribbon diagrams in all figures were drawn with PyMOL (22).

Figure 3.
Fig. 3. Active site formation of Rv1264. (A) Schematic diagram of domain rearrangements upon activation. Regulatory and catalytic domains are labeled N and C, respectively. Numbers in Å2 refer to buried surface areas between domains. (B) Superposition of the active sites of Rv1264 (active conformation, green with black labels) and a mammalian AC (19) (1CJK, yellow with gray labels). ATP was modeled into Rv1264 by superposition with ATP S-R[P] of 1CJK. The side chains of seven key residues, ATP, and sulfate are shown in stick representation with oxygen, red; nitrogen, blue; phosphate, mauve; sulfur, orange; and Mg2+ and Mn2+, light blue. (A) and (B) after residue names refer to the two monomers. (C) Surface representation of the catalytic domains of Rv1264 in the inhibited (blue) and active (green) states. Activesite residues for one active site are shown in stick representation. For clarity, residues from the second of the two identical active sites are shown as lines. (D) Detailed view of the 1-switch region (red) from a superposition of the catalytic domains of the active (green) and inhibited (blue) states of Rv1264 (rmsd of 1.66 Å over 157 out of 163 C atoms).

The above figures are reprinted by permission from the AAAs: Science (2005, 308, 1020-1023) copyright 2005.

Figures were selected by the author.