Catalyzes the condensation of pyruvate and acetyl-coenzyme A to form (R)-citramalate (PubMed:15292141, PubMed:18498255, PubMed:19351325). Shows strict substrate specificity for pyruvate. Cannot use alpha-ketoisovalerate, alpha-ketobutyrate, alpha-ketoisocaproate, alpha-ketoglutarate or glyoxylate (PubMed:15292141, PubMed:18498255). acetyl-CoA + H2O + pyruvate = (3R)-citramalate + CoA + H(+) Mn(2+) is the most effective activator, followed by Co(2+), Ca(2+), Mg(2+) and Ni(2+). Regulated by the end-product isoleucine via a feedback inhibition. The binding of isoleucine has inhibitory effects on the binding of both pyruvate and acetyl-CoA. May act via conformational change of the dimer interface of the regulatory domain, leading to inhibition of the catalytic reaction. kcat is 2.41 sec(-1) (PubMed:15292141). kcat is 10.3 sec(-1) with acetyl-CoA as substrate (PubMed:18498255). kcat is 9.13 sec(-1) with pyruvate as substrate (PubMed:18498255). Optimum temperature is 35-40 degrees Celsius. Amino-acid biosynthesis; L-isoleucine biosynthesis; 2-oxobutanoate from pyruvate: step 1/3. Homodimer. Expression is repressed by isoleucine but not by leucine. Contains a catalytic N-terminal domain and a C-terminal regulatory domain, linked together by a flexible region (PubMed:18498255, PubMed:19351325). The catalytic domain consists of a TIM barrel flanked by an extended C-terminal region. The active site is located at the center of the TIM barrel near the C-terminal ends of the beta-strands and is composed of conserved residues of the beta-strands of one subunit and the C-terminal region of the other (PubMed:18498255). Belongs to the alpha-IPM synthase/homocitrate synthase family.