We are developing computational methods that can expand our understanding of the atomic-level detail of the active site of proteins, focusing on the Arsenate Reductase (ArsC) superfamily. Global arsenic concentrations in water, soil and rice have been rising, especially due to increased pollutants resulting from mining and agricultural activities. ArsC proteins are vital within arsenic redox microorganisms that lower the concentrations of arsenate and are, therefore, important in the bioremediation strategies that prevent arsenic, a highly toxic and carcinogenic metalloid, from reaching alarming levels in the environment. Our research utilizes Multi-level Iterative Sequence Searching Technique (MISST), a method which uses the functional site profiles from structurally known proteins to computationally characterize members of protein groups and then uses an active site profiler tool, Deacon Active Site Profiler (DSAP), to enlarge the groups using data from GenBank. One goal of the project is to validate the MISST process by confirming the divisions of the superfamily with previously published groups. Our project also focuses on characterizing the active site geometry using molecular dynamics. This part of the project will allow us to hypothesize the enzyme reaction mechanism within and between each isofunctional family. We hypothesize that the ArsC superfamily, previously thought of as two or three ambiguous groups, should in fact be six isofunctional groups. Several of these groups have stark similarities to protein tyrosine phosphatases (PTP). Further investigation suggests that six proteins have domains containing active sites similar to both ArsC and PTP. Our research will provide insight into the molecular functional details of each of the six ArsC isofunctional families that we have identified. Our computational methods can be applied to any subfamily within a superfamily, providing an efficient means of identifying functionally and structurally similar proteins.

Functionally relevant clustering of the arsenate reductase (ArsC) superfamily

2019 Spring National Meeting

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