Biology subjects

Tse, E. C. M.

Publications and source records attributed to Tse, E. C. M..

2 recordsLinked to original sources

bioRxiv2023

Combinatorial in silico approach for cancer-associated 4Fe-4S protein discovery

Iron-sulfur (Fe-S) proteins play vital roles in multiple cellular processes, including mediating redox balance as well as DNA replication and repair. Given the role of Fe-S cofactors in genome maintenance, mutations in such metalloproteins could be associated with cancer. Nevertheless, only a few cancer-associated Fe-S proteins have been identified. In vitro, Fe-S cluster is susceptible to degradation in oxic environment. It could also be replaced by other metal ions during protein purification, mis-labelled as zinc finger or Zn-containing proteins. In silico, bioinorganic Fe-S cluster lacks unique sequence characteristics that distinguish itself from other metal-coordination sites, making motif prediction based solely on protein sequence difficult. Thus, in this study, three traits have been employed to discover putative cancer-associated 4Fe-4S proteins. Here, we have analyzed the human proteome via a three-pronged approach: (i) the presence of a triamino acid motif, (ii) the geometric arrangements of the cysteines, and (iii) the mutations of cancer-associated cysteines. In addition to MUTYH, a known 4Fe-4S human DNA glycosylase, 21 novel proteins were discovered as potential cancer-associated 4Fe-4S proteins. While 6 receptor proteins and 3 growth factors have been identified as potential targets in this study, 5 histone lysine methyltransferases with SET domains were also predicted to contain 4Fe-4S metallocofactors. This work provides insights for rational adjustments in experimental design and novel cancer biomarker discovery.

bioinformatics↗

bioRxiv2019

Extracellular DNA promotes efficient extracellular electron transfer by pyocyanin in Pseudomonas aeruginosa biofilms

Extracellular electron transfer (EET), the process whereby cells access electron acceptors or donors that reside many cell lengths away, enables metabolic activity by microorganisms, particularly under oxidant-limited conditions that occur in multicellular bacterial biofilms. Although different mechanisms underpin this process in select organisms, a widespread strategy involves extracellular electron shuttles, redox-active metabolites that are secreted and recycled by diverse bacteria. How these shuttles catalyze electron transfer within biofilms without being lost to the environment has been a long-standing question. Here, we show that phenazine electron shuttles mediate efficient EET through interactions with extracellular DNA (eDNA) in Pseudomonas aeruginosa biofilms, which are important in nature and disease. Retention of pyocyanin (PYO) and phenazine carboxamide in the biofilm matrix is facilitated by binding to eDNA. In vitro, different phenazines can exchange electrons in the presence or absence of DNA and phenazines can participate directly in redox reactions through DNA; the biofilm eDNA can also support rapid electron transfer between redox active intercalators. Electrochemical measurements of biofilms indicate that retained PYO supports an efficient redox cycle with rapid EET and slow loss from the biofilm. Together, these results establish that eDNA facilitates phenazine metabolic processes in P. aeruginosa biofilms, suggesting a model for how extracellular electron shuttles achieve retention and efficient EET in biofilms.

microbiology↗