PDBsum entry: 1tv7

Ligand binding protein

PDB-id: 1tv7

Biological unit* = asymmetric unit, as shown
(*as deduced by PQS)

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Description

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PROCHECK

Protein chains

327 a.a. *

Ligands

SO4 ×2

SF4 ×4

Waters ×64

* Residue conservation analysis

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Clefts Calculation

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PDB id:

1tv7

Name:

Ligand binding protein

Title:

Structure of the s-adenosylmethionine dependent enzyme moaa

Structure:

Molybdenum cofactor biosynthesis protein a. Chain: a, b. Synonym: moaa. Engineered: yes

Source:

Staphylococcus aureus. Organism_taxid: 1280. Strain: n315 or mw2. Gene: moaa. Expressed in: escherichia coli. Expression_system_taxid: 562.

Biological unit:

Dimer (from PQS)

UniProt:

Chains A, B: P65388 (MOAA_STAAN)

Seq:

Struc:

Seq:

340 a.a.

Struc:

327 a.a.

Key:	PfamA domain
Secondary structure	CATH domain

Resolution:

2.80Å

R-factor:

0.189

R-free:

0.211

Authors:

P.Haenzelmann,H.Schindelin

Key ref:

P.Hänzelmann and H.Schindelin (2004). Crystal structure of the S-adenosylmethionine-dependent enzyme MoaA and its implications for molybdenum cofactor deficiency in humans.. Proc Natl Acad Sci U S A, 101, 12870-12875. [PubMed id: 15317939] [DOI: 10.1073/pnas.0404624101]

Date:

28-Jun-04

Release date:

31-Aug-04

Related entries:

1tv8

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Clefts

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Key reference

DOI no: 10.1073/pnas.0404624101

Proc Natl Acad Sci U S A 101:12870-12875 (2004)

PubMed id: 15317939

Crystal structure of the S-adenosylmethionine-dependent enzyme MoaA and its implications for molybdenum cofactor deficiency in humans.

P.Hänzelmann, H.Schindelin.

ABSTRACT

The MoaA and MoaC proteins catalyze the first step during molybdenum cofactor biosynthesis, the conversion of a guanosine derivative to precursor Z. MoaA belongs to the S-adenosylmethionine (SAM)-dependent radical enzyme superfamily, members of which catalyze the formation of protein and/or substrate radicals by reductive cleavage of SAM by a [4Fe-4S] cluster. A defined in vitro system is described, which generates precursor Z and led to the identification of 5'-GTP as the substrate. The structures of MoaA in the apo-state (2.8 angstroms) and in complex with SAM (2.2 angstroms) provide valuable insights into its mechanism and help to define the defects caused by mutations in the human ortholog of MoaA that lead to molybdenum cofactor deficiency, a usually fatal disease accompanied by severe neurological symptoms. The central core of each subunit of the MoaA dimer is an incomplete triosephosphate isomerase barrel formed by the N-terminal part of the protein, which contains the [4Fe-4S] cluster typical for SAM-dependent radical enzymes. SAM is the fourth ligand to the cluster and binds to its unique Fe as an N/O chelate. The lateral opening of the incomplete triosephosphate isomerase barrel is covered by the C-terminal part of the protein containing an additional [4Fe-4S] cluster, which is unique to MoaA proteins. Both FeS clusters are separated by approximately 17 angstroms, with a large active site pocket between. The noncysteinyl-ligated unique Fe site of the C-terminal [4Fe-4S] cluster is proposed to be involved in the binding and activation of 5'-GTP.

Selected figure(s)

Figure 4.
Fig. 4. Location of missense mutations detected in Moco-deficient patients. Secondary structure elements and cofactors are rendered transparent. Human mutations, FeS clusters, and SAM are shown as ball and stick.

Figure 5.
Fig. 5. Structural comparison of SAM-dependent radical enzymes and reactions catalyzed. -Helices are colored in orange, -sheets are colored in blue, and turns are colored in gray. Nonstructurally conserved secondary structural elements are rendered transparent. FeS clusters and substrates are shown in ball and stick.

Figures were selected by an automated process.