Search Results

You searched for all publications:

with publication states 'Published (Approved)'
published in journal 'Acs Bio & Med Chem Au'

Search Again...

These results only include publications that have been reviewed and processed by Diamond Light Source. To also view papers that have not yet been processed click here.

You can use the folder icon under Actions to collate papers as required. You can then click on View Folder in the left-hand navigation to review and/or download your folder.

Exact matches
Related results

4 items found (0 items not approved), displaying all items.1

Instruments / Technical Area	Publication Details	Published
I03-Macromolecular Crystallography	Bioinformatics-facilitated identification of novel bacterial sulfoglycosidases that hydrolyze 6-sulfo-N-acetylglucosamine Mochen Dong , Zhuoyun Chen , Yuan He , Rémi Zallot , Yi Jin Acs Bio & Med Chem Au DOI: 10.1021/acsbiomedchemau.4c00088 Diamond Proposal Number(s): [31850] Open Access Show Abstract ▼ Abstract: Glycan sulfation is a widespread postglycosylation modification crucial for modulating biological functions including cellular adhesion, signaling, and bacterial colonization. 6-Sulfo-β-GlcNAcases are a class of enzyme that alters sulfation patterns. Such changes in sulfation patterns are linked to diseases such as bowel inflammation, colitis, and cancer. Despite their significance, 6-sulfo-β-GlcNAcases, which cleave β-linked 6-sulfo-N-acetylglucosamine (6S-GlcNAc), have been but rarely identified. This scarcity results mainly from the short, diverse, and distinctive sulfate-binding motifs required for recognition of the 6-sulfate group in 6S-GlcNAc in addition to the conserved GH20 family features. In this study, we discovered 6-sulfo-β-GlcNAcases and assigned two novel sulfate-binding motifs by the use of comparative genomics, structural predictions, and activity-based screening. Our findings expand the known microbiota capable of degrading sulfated glycans and add significant enzymes to the tool kit for analysis and synthesis of sulfated oligosaccharides.	Nov 2024
I04-Macromolecular Crystallography	Ciprofloxacin inhibits Angiotensin I-Converting Enzyme (ACE) activity by binding at the exosite, distal to the catalytic pocket Kyle S. Gregory , Vinasha Ramasamy , Edward D. Sturrock , K. Ravi Acharya Acs Bio & Med Chem Au 5 DOI: 10.1021/acsbiomedchemau.5c00089 Diamond Proposal Number(s): [23269] Open Access Show Abstract ▼ Abstract: Human somatic angiotensin I-converting enzyme is a key zinc metallopeptidase in cardiovascular regulation that hydrolyzes angiotensin peptides (Ang I, Ang II), as well as other vasoactive peptides, including kinins (e.g., bradykinin), substance P, the acetylated tetrapeptide Ac-Ser-Asp-Lys-Pro, and the amyloid ß-peptide. Because of its enzymatic promiscuity, ACE and its substrates and products affect many physiological processes, including blood pressure control, hemopoiesis, reproduction, renal development/function, fibrosis, and immune response. ACE inhibitors are among the most important therapeutic agents available today for the treatment of hypertension, heart failure, coronary artery disease, renal insufficiency, and general atherosclerosis. However, they need much improvement because of the side effects seen in patients with long-term treatment due to nonselective inhibition of the N- and C-domains of ACE (referred to as nACE and cACE, respectively). Here, we report that ACE activity can be inhibited by ciprofloxacin, a potent fluoroquinolone antibiotic (IC50 202.7/Ki 33.8 μM for cACE). In addition, the high-resolution crystal structure of cACE in complex with ciprofloxacin reveals that it binds at an exosite away from the active site pocket, overlapping the position of a potential allosteric site with a different binding mode. The detailed structural information reported here will provide a useful scaffold for the design of future potent allosteric inhibitors.	Jun 2025
I03-Macromolecular Crystallography	Deciphering the synthetic and refolding strategy of a cysteine-rich domain in the tumor necrosis factor receptor (TNF-R) for racemic crystallography analysis and D-peptide ligand discovery Alexander J. Lander , Yifu Kong , Yi Jin , Chuanliu Wu , Louis Y. P. Luk Acs Bio & Med Chem Au DOI: 10.1021/acsbiomedchemau.3c00060 Diamond Proposal Number(s): [20147] Open Access Show Abstract ▼ Abstract: Many cell-surface receptors are promising targets for chemical synthesis because of their critical roles in disease development. This synthetic approach enables investigations by racemic protein crystallography and ligand discovery by mirror-image methodologies. However, due to their complex nature, the chemical synthesis of a receptor can be a significant challenge. Here, we describe the chemical synthesis and folding of a central, cysteine-rich domain of the cell-surface receptor tumor necrosis factor 1 which is integral to binding of the cytokine TNF-α, namely, TNFR-1 CRD2. Racemic protein crystallography at 1.4 Å confirmed that the native binding conformation was preserved, and TNFR-1 CRD2 maintained its capacity to bind to TNF-α (KD ≈ 7 nM). Encouraged by this discovery, we carried out mirror-image phage display using the enantiomeric receptor mimic and identified a d-peptide ligand for TNFR-1 CRD2 (KD = 1 μM). This work demonstrated that cysteine-rich domains, including the central domains, can be chemically synthesized and used as mimics for investigations.	Dec 2023
I04-Macromolecular Crystallography	Structure of the D-cycloserine-resistant variant D322N of alanine racemase from Mycobacterium tuberculosis Cesira De Chiara , Gareth A. Prosser , Roksana Ogrodowicz , Luiz P. S. De Carvalho Acs Bio & Med Chem Au 5 DOI: 10.1021/acsbiomedchemau.2c00074 Diamond Proposal Number(s): [13775, 18566] Open Access Show Abstract ▼ Abstract: Alanine racemase (Alr) is a pyridoxal 5′-phosphate-dependent enzyme that catalyzes the racemization of l-alanine to d-alanine. Alr is one of the two targets of the broad-spectrum antibiotic d-cycloserine (DCS), a structural analogue of d-alanine. Despite being an essential component of regimens used to treat multi- and extensively drug-resistant tuberculosis for almost seven decades, resistance to DCS has not been observed in patients. We previously demonstrated that DCS evades resistance due to an ultralow rate of emergence of mutations. Yet, we identified a single polymorphism (converting Asp322 to Asn) in the alr gene, which arose in 8 out of 11 independent variants identified and that confers resistance. Here, we present the crystal structure of the Alr variant D322N in both the free and DCS-inactivated forms and the characterization of its DCS inactivation mechanism by UV–visible and fluorescence spectroscopy. Comparison of these results with those obtained with wild-type Alr reveals the structural basis of the 240-fold reduced inhibition observed in Alr D322N.	Mar 2023

Publications Database

Search Results

You searched for all publications:

Search Again...

Subject Areas (check all that apply) select all

Instruments used to collect data (check all that apply) select all

Collaborations involved (check all that apply) select all

Diamond Offline Facilities used

Relevant Technical Areas (check all that apply) select all

Menu for Anonymous User