Andrew C Marshall- PhD
- Research Associate at The University of Western Australia
Andrew C Marshall
- PhD
- Research Associate at The University of Western Australia
About
21
Publications
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Introduction
I’m passionate about relating protein structure to function and using this information to: (1) better understand how life functions at a molecular level, and (2) inform the design of new molecules to address biomedical or biotechnological problems. I have had the privilege of working on a wide variety of proteins, ranging from microbial enzymes to mammalian nucleic acid binding proteins; gaining expertise in protein purification, X-ray crystallography & other biochemical/biophysical techniques.
Current institution
Additional affiliations
January 2019 - January 2019
Publications
Publications (21)
Heterogeneous nuclear ribonucleoprotein K (hnRNPK) is an RNA-binding protein containing low-complexity domains (LCDs), which are known to regulate protein behavior under stress conditions. This study demonstrates the ability to control hnRNPK’s transitions into four distinct material states—monomer, soluble aggregate, liquid droplet, and fibrillar...
Heterogeneous nuclear ribonuclear protein K (hnRNPK) is an RNA-binding protein with low-complexity domains (LCDs) that regulate its behavior under stress conditions. This study demonstrates the ability to control hnRNPK’s transitions into four distinct material states—monomer, soluble aggregate, liquid droplet, and fibrillar hydrogel—by modulating...
The proteins SFPQ (splicing Factor Proline/Glutamine rich) and NONO (non-POU domain-containing octamer-binding protein) are mammalian members of the Drosophila Behaviour/Human Splicing (DBHS) protein family, which share 76% sequence identity in their conserved 320 amino acid DBHS domain. SFPQ and NONO are involved in all steps of post-transcription...
A new high-pressure single-crystal diffraction setup has been designed and implemented at the Australian Synchrotron for collecting molecular and protein crystal structures. The setup incorporates a modified micro-Merrill–Bassett cell and holder designed specifically to fit onto the horizontal air-bearing goniometer, allowing high-pressure diffract...
Demixing of proteins and nucleic acids into condensed liquid phases is rapidly emerging as a ubiquitous mechanism governing the organisation of molecules within the cell. Long disordered low complexity regions (LCRs) are a common feature of proteins that form biomolecular condensates. RNA-binding proteins with prion-like composition have been highl...
High-risk neuroblastoma patients have poor survival rates and require better therapeutic options. High expression of a multifunctional DNA and RNA-binding protein, NONO, in neuroblastoma is associated with poor patient outcome; however, there is little understanding of the mechanism of NONO-dependent oncogenic gene regulatory activity in neuroblast...
RNA-binding proteins of the DBHS (Drosophila Behavior Human Splicing) family, NONO, SFPQ, and PSPC1 have numerous roles in genome stability and transcriptional and post-transcriptional regulation. Critical to DBHS activity is their recruitment to distinct subnuclear locations, for example paraspeckle condensates, where DBHS proteins bind to the lon...
The recombination directionality factors from Mesorhizobium spp. (RdfS) are involved in regulating the excision and transfer of integrative and conjugative elements. Here, solution small-angle X-ray scattering, and crystallization and preliminary structure solution of RdfS from Mesorhizobium japonicum R7A are presented. RdfS crystallizes in space g...
High-risk neuroblastoma patients have poor survival rates and require better therapeutic options. High expression of a multifunctional DNA and RNA binding protein, NONO, in neuroblastoma is associated with poor patient outcome, however there is little understanding of the mechanism of NONO-dependent oncogenic gene regulatory activity in neuroblasto...
The Drosophila behaviour/human splicing (DBHS) proteins are a family of RNA/DNA binding cofactors liable for a range of cellular processes. DBHS proteins include the non-POU domain-containing octamer-binding protein (NONO) and paraspeckle protein component 1 (PSPC1), proteins capable of forming combinatorial dimers. Here, we describe the crystal st...
Activation of enzymes by monovalent cations (M+) is a widespread phenomenon in biology. Despite this, there are few structure-based studies describing the underlying molecular details. Thiolases are a ubiquitous and highly conserved family of enzymes containing both K+-activated and K+-independent members. Guided by structures of naturally occurrin...
Here we report the design, synthesis, and evaluation of a series of inhibitors of S. aureus BPL (SaBPL), where the central acylphosphate of the natural intermediate biotinyl-5’-AMP (1) is replaced by a sulfonamide isostere. Acylsulfamide (6) and amino sulfonylurea (7) showed potent in vitro inhibitory activity (Ki = 0.007 0.003 and 0.065 0.03 µ...
Aspergillus fumigatus infections are associated with high mortality rates and high treatment costs. Limited available antifungals and increasing antifungal resistance highlight an urgent need for new antifungals. Thioredoxin reductase (TrxR) is essential for maintaining redox homeostasis and presents as a promising target for novel antifungals. We...
Chymotrypsin is a protease that is commonly used as a standard for protein crystallization and as a model system for studying serine proteases. Unliganded bovine α-chymotrypsin was crystallized at neutral pH using ammonium sulphate as the precipitant, resulting in crystals that conform to P65 symmetry with unit cell parameters that have not been re...
A series of dipeptide aldehydes containing different N-terminal heterocycles was prepared and assayed in vitro against α-chymotrypsin to ascertain the importance of the heterocycle in maintaining a β-strand geometry while also providing a hydrogen bond donor equivalent to the backbone amide nitrogen of the surrogate amino acid. The dipeptide contai...
Peroxisome proliferator activated receptor γ (PPARγ) is a nuclear receptor and target for antidiabetics that increase insulin sensitivity. Owing to the side effects of PPARγ full agonists, research has recently focused on non-activating ligands of PPARγ, which increase insulin sensitivity with decreased side effects. Here, we present the crystal st...
Cytosolic thiolase (CT) catalyzes the reversible Claisen condensation of two molecules of acetyl-CoA to produce acetoacetyl-CoA. The reaction cycle proceeds via a ping-pong mechanism involving an acetylated enzyme intermediate and two separate oxyanion holes which stabilize negatively charged reaction intermediates. This is the initial step in the...
Questions
Question (1)
Hi all, I'm working on an enzyme that has enhanced activity in the presence of monovalent cations (MVC). Addition of either Na+ or K+ decreases the Km for substrate to the same degree (Km = 8 uM for both; Km = 25 uM in absence of MVCs), but kcat is increased to a greater extent for K+ than for Na+. Could this be correctly interpreted as both increasing substrate affinity to the same degree, but K+ is more effective at promoting catalysis? I realise that Km is related to, but not equivalent to affinity, so I'm unsure whether my interpretation is too simplistic..?
Thanks,
Andrew
