Olga Salamakha
Pronouns: she/her
Research Mentor(s): Ruma Banerjee
Research Mentor School/College/Department: Biological Chemistry / Medicine
Program:
Authors: Olga Salamakha
Session: Session 7: 4:40 pm – 5:30 pm
Poster: 35
Abstract
Vitamin B12 is a tetrapyrrole, consisting of a central cobalt ion coordinated by four nitrogens in the corrin ring. Attached to the edge of the corrin ring is 5,6-dimethylbenzimidazole (DMB), which serves as the lower axial ligand to the cobalt ion in solution. The upper axial ligand can vary. Vitamin B12 is used as a cofactor by mitochondrial methylmalonylCoA mutase (MMUT) and cytoplasmic methionine synthase. Vitamin B12 is not found in large quantities, and mammals have an elaborate multi-protein system for trafficking vitamin B12. In the mitochondrial part of the pathway, the chaperones and transporters that work in processing this cofactor are the ATP-dependent cob(I)alamin adenosyltransferase (MMAB) and the G Protein MMAA. MMAB is responsible for synthesis of adenosylcobalamin (AdoCbl), the active cofactor form used by MMUT. MMAB also delivers AdoCbl to MMUT and is involved in repair of inactive MMUT. In MMAB, the lower DMB ligand of AdoCbl is found in a tucked in conformation close to the corrin ring but not coordinating to the cobalt ion. In the MMAB homolog from Mycobacterium tuberculosis, the DMB tail is bound in a distinct binding pocket, which we hypothesize is important for selectivity of cofactor transfer. In this study, we have introduced mutations in residues lining the DMB pocket and examined their effect on cofactor binding affinity and transfer from MMAB to MMUT.
