Bir A, Escherichia coli

The E. coli BirA protein performs different functions depending on its dimeric state [40]. As a heterodimer with biotin carboxyl carrier protein (BCCP), a subunit of acetyl-CoA carboxylase, it functions as a biotin protein ligase (Function 1); as a homodimer, it functions as a biotin operon repressor (Function 2) that binds to DNA [59]. The BirA structure consists of three domains: an a-orthogonal bundle, an a/p 2-layer sandwich domain and a mainly p SH3-type fold (Fig. 2.7). The residues responsible for the two functions of BirA are located in distinct sites in the protein. The catalytic residues for the ligase activity of the protein are Arg118, Lys183, and Arg317, and are found in a pocket formed between the ap sandwich, the SH3 domain, and a helix-turn-helix (H-T-H) motif (residues 22-46) which is responsible for the binding DNA found in the a-orthogonal bundle (Fig. 2.7) [40].

Malate synthase

Figure 2.6 Malate synthase. The enzyme active site is shown in blue and the laminin- binding site is shown in red. Different domains are shown in different colors (PDB:2GQ3). (See color plate section for the color representation of this figure.)

BirA. The catalytic site residues are shown in blue while the H-T-H motif involved in

Figure 2.7 BirA. The catalytic site residues are shown in blue while the H-T-H motif involved in

binding DNA (moonlighting function) is shown in red. Different domains are shown in

different colors (PDB:1BIB). (See color plate section for the color representation of this figure.)

MRDI, Homo sapiens

The protein mediator of RhoA-dependent invasion (MRDI) is a moonlighting protein found in humans [41]. It acts both as a methylthioribose-1-phosphate (MTR-1-P) isomerase (EC 5.3.1.23) (Function 1) and a mediator of melanoma cell invasion (Function 2). The MRDI structure consists of two chains, each comprising a 4-helix bundle and a Rossmann fold (Fig. 2.8). The catalytic residues of MRDI are Cys168 and Asp248 (shown in blue), which are located in the base of a pocket.

A potential binding site has been identified in MRDI by mutational analysis: Ser283 and Arg109 (shown in red). This is located distinct from the catalytic site in another pocket of the protein, formed between the two domains of each chain.

 
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