PDBsum entry 2v7q

Hydrolase

PDB id: 2v7q

Contents

Protein chains

487 a.a. *

469 a.a. *

263 a.a. *

131 a.a. *

47 a.a. *

43 a.a. *

Ligands

ATP ×3

ADP ×2

PO4

Metals

_MG ×5

Waters ×1940

* Residue conservation analysis

PDB id:

2v7q

Name:

Hydrolase

Title:

The structure of f1-atpase inhibited by i1-60his, a monomeric form of the inhibitor protein, if1.

Structure:

Atp synthase subunit alpha heart isoform. Chain: a, b, c. Fragment: residues 44-553. Synonym: atp synthase alpha chain heart isoform. Atp synthase subunit beta. Chain: d, e, f. Fragment: residues 47-528. Synonym: atp synthase beta chain. Atp synthase gamma chain.

Source:

Bos taurus. Cow. Organism_taxid: 9913. Organ: heart. Tissue: muscle. Expressed in: escherichia coli. Expression_system_taxid: 469008.

Resolution:

2.10Å R-factor: 0.193 R-free: 0.245

Authors:

J.R.Gledhill,M.G.Montgomery,A.G.W.Leslie,J.E.Walker

Key ref:

J.R.Gledhill et al. (2007). How the regulatory protein, IF(1), inhibits F(1)-ATPase from bovine mitochondria. Proc Natl Acad Sci U S A, 104, 15671-15676. PubMed id: 17895376 DOI: 10.1073/pnas.0707326104

Date:

31-Jul-07 Release date: 18-Sep-07

Protein chains

P19483  (ATPA_BOVIN) -  ATP synthase subunit alpha, mitochondrial from Bos taurus

Seq: 553 a.a.

Struc: 487 a.a.

Protein chains

P00829  (ATPB_BOVIN) -  ATP synthase subunit beta, mitochondrial from Bos taurus

Seq: 528 a.a.

Struc: 469 a.a.

Protein chain

P05631  (ATPG_BOVIN) -  ATP synthase subunit gamma, mitochondrial from Bos taurus

Seq: 298 a.a.

Struc: 263 a.a.

Protein chain

P05630  (ATPD_BOVIN) -  ATP synthase subunit delta, mitochondrial from Bos taurus

Seq: 168 a.a.

Struc: 131 a.a.

Protein chain

P05632  (ATP5E_BOVIN) -  ATP synthase subunit epsilon, mitochondrial from Bos taurus

Seq: 51 a.a.

Struc: 47 a.a.

Protein chain

P01096  (ATIF1_BOVIN) -  ATPase inhibitor, mitochondrial from Bos taurus

Seq: 109 a.a.

Struc: 43 a.a.

Enzyme reactions

• Enzyme class 2: Chains A, B, C, H, I: E.C.3.6.1.14 - adenosine-tetraphosphatase.
• Reaction: adenosine 5'-tetraphosphate + H2O = phosphate + ATP + H⁺

adenosine 5'-tetraphosphate (Bound ligand (Het Group name = ATP) corresponds exactly) + H2O = phosphate + ATP + H(+)

• Enzyme class 3: Chains D, E, F: E.C.7.1.2.2 - H(+)-transporting two-sector ATPase.
• Reaction: ATP + H2O + 4 H⁺(in) = ADP + phosphate + 5 H⁺(out)
• Enzyme class 4: Chain G: E.C.3.6.1.34 - Transferred entry: 7.1.2.2.

Note, where more than one E.C. class is given (as above), each may correspond to a different protein domain or, in the case of polyprotein precursors, to a different mature protein.

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

reference

DOI no: 10.1073/pnas.0707326104

Proc Natl Acad Sci U S A 104:15671-15676 (2007)

PubMed id: 17895376

How the regulatory protein, IF(1), inhibits F(1)-ATPase from bovine mitochondria.

J.R.Gledhill, M.G.Montgomery, A.G.Leslie, J.E.Walker.

ABSTRACT

The structure of bovine F(1)-ATPase inhibited by a monomeric form of the inhibitor protein, IF(1), known as I1-60His, lacking most of the dimerization region, has been determined at 2.1-A resolution. The resolved region of the inhibitor from residues 8-50 consists of an extended structure from residues 8-13, followed by two alpha-helices from residues 14-18 and residues 21-50 linked by a turn. The binding site in the beta(DP)-alpha(DP) catalytic interface is complex with contributions from five different subunits of F(1)-ATPase. The longer helix extends from the external surface of F(1) via a deep groove made from helices and loops in the C-terminal domains of subunits beta(DP), alpha(DP), beta(TP), and alpha(TP) to the internal cavity surrounding the central stalk. The linker and shorter helix interact with the gamma-subunit in the central stalk, and the N-terminal region extends across the central cavity to interact with the nucleotide binding domain of the alpha(E) subunit. To form these complex interactions and penetrate into the core of the enzyme, it is likely that the initial interaction of the inhibitor with F(1) forms via the open conformation of the beta(E) subunit. Then, as two ATP molecules are hydrolyzed, the beta(E)-alpha(E) interface converts to the beta(DP)-alpha(DP) interface via the beta(TP)-alpha(TP) interface, trapping the inhibitor progressively in its binding site and a nucleotide in the catalytic site of subunit beta(DP). The inhibition probably arises by IF(1) imposing the structure and properties of the beta(TP)-alpha(TP) interface on the beta(DP)-alpha(DP) interface, thereby preventing it from hydrolyzing the bound ATP.

Selected figure(s)

Figure 1.
Fig. 1. The structure of the bovine F[1]-I1–60His complex. (A) Overall view of the complex. The -, -, -, -, and -subunits are shown in ribbon form in red, yellow, dark blue, magenta, and green, respectively. Residues 8–50 of I1–60His are shown in light blue solid representation. (B) View upward (away from the foot of the central stalk), along the axis of the -subunit showing the orientation of the long -helix of I1–60His relative to the C-terminal domains of the - and -subunits. The N- and C-terminal ends of the I1–60His are labeled N and C, respectively.

Figure 2.
Fig. 2. The binding site for I1–60His in bovine F[1]-ATPase. (A and B) Ribbon and solid representations, respectively, of the binding site groove formed from -helices and loops between them in the C-terminal domains of the [DP]-, [DP]-, and [TP]- subunits, occupied by the long helix (residues 21–50) of I1–60His (light blue). The N- and C-terminal ends of the I1–60HIS are labeled N and C, respectively, in A. (B) The orange side chains are those of the strictly conserved residues Lys-24, Arg-25, and Glu-26 of I1–60His that do not interact with F[1]-ATPase. (C and D) Interactions between residues 8–46 and F[1]-ATPase. (C) View from the side of the central stalk showing the orientation of I1–60His relative to the -subunit. The N- and C-terminal ends of the I1–60HIS are labeled N and C, respectively. (D) View down along the axis of the -subunit showing the interaction of the short helix with the -subunit and the interaction between the extended region formed by residues 10–12 of I1–60His and side chains in the nucleotide binding domain of the [E]-subunit.

Figures were selected by an automated process.