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Biosynthesis of D-alanyl-lipoteichoic acid: the tertiary structure of apo-D-alanyl carrier protein. Biochemistry 2001 Jul 10;40(27):7964-72

Date

07/04/2001

Pubmed ID

11434765

DOI

10.1021/bi010355a

Scopus ID

2-s2.0-0035838447   37 Citations

Abstract

The D-alanylation of lipoteichoic acid (LTA) allows the Gram-positive organism to modulate its surface charge, regulate ligand binding, and control the electromechanical properties of the cell wall. The incorporation of D-alanine into LTA requires the D-alanine:D-alanyl carrier protein ligase (AMP-forming) (Dcl) and the carrier protein (Dcp). The high-resolution solution structure of the 81-residue (8.9 kDa) Dcp has been determined by multidimensional heteronuclear NMR. An ensemble of 30 structures was calculated using the torsion angle dynamics approach of DYANA. These calculations utilized 3288 NOEs containing 1582 unique nontrivial NOE distance constraints. Superposition of residues 4-81 on the mean structure yields average atomic rmsd values of 0.43 +/- 0.08 and 0.86 +/- 0.09 A for backbone and non-hydrogen atoms, respectively. The solution structure is composed of three alpha-helices in a bundle with additional short 3(10)- and alpha-helices in intervening loops. Comparisons of the three-dimensional structure with the acyl carrier proteins involved in fatty acid, polyketide, and nonribosomal peptide syntheses support the conclusion that Dcp is a homologue in this family. While there is conservation of the three-helix bundle fold, Dcp has a higher enthalpy of unfolding and no apparent divalent metal binding site(s), features that distinguish it from the fatty acid synthase acyl carrier protein of Escherichia coli. This three-dimensional structure also provides insights into the D-alanine ligation site recognized by Dcl, as well as the site which may bind the poly(glycerophosphate) acceptor moiety of membrane-associated LTA.

Author List

Volkman BF, Zhang Q, Debabov DV, Rivera E, Kresheck GC, Neuhaus FC

Author

Brian F. Volkman PhD Professor in the Biochemistry department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Acyl Carrier Protein
Amino Acid Sequence
Apoproteins
Bacterial Proteins
Binding Sites
Calcium
Calorimetry, Differential Scanning
Carrier Proteins
Circular Dichroism
Hydrogen Bonding
Molecular Sequence Data
Nuclear Magnetic Resonance, Biomolecular
Protein Denaturation
Protein Structure, Secondary
Protein Structure, Tertiary
Sequence Homology, Amino Acid
Teichoic Acids
Thermodynamics
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