Compositions and methods comprising polynucleotides and polypeptides having ALS activity and tolerance to at least one ALS inhibitor are provided. In specific embodiments, the sequence has an increased preference for 2-ketobutyrate, when compared to an appropriate control, such as for example, HRA, and/or a preference for 2-ketobutyrate similar to a native ALS. Further provided are nucleic acid constructs, plants, plant cells, explants, seeds and grain having the ALS inhibitor tolerant sequences. Various methods of employing the ALS inhibitor tolerant sequences are provided. Such methods include methods for producing an ALS inhibitor tolerant plant, plant cell, explant or seed and methods of controlling weeds in a field containing a crop employing the plants and/or seeds disclosed herein.