Martin Middleditch

ORCID: 0000-0001-7077-5897
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About
Contact & Profiles
Research Areas
  • Enzyme Structure and Function
  • Biochemical and Structural Characterization
  • X-ray Diffraction in Crystallography
  • Streptococcal Infections and Treatments
  • Crystallization and Solubility Studies
  • Advanced Proteomics Techniques and Applications
  • Biochemical and Molecular Research
  • Cardiovascular Function and Risk Factors
  • Cancer, Hypoxia, and Metabolism
  • Tuberculosis Research and Epidemiology
  • Pancreatic function and diabetes
  • Amino Acid Enzymes and Metabolism
  • Extracellular vesicles in disease
  • Cell Adhesion Molecules Research
  • Growth Hormone and Insulin-like Growth Factors
  • Fibroblast Growth Factor Research
  • Plant-Microbe Interactions and Immunity
  • Bee Products Chemical Analysis
  • Legume Nitrogen Fixing Symbiosis
  • MicroRNA in disease regulation
  • Advanced Glycation End Products research
  • Insect and Pesticide Research
  • Neonatal and Maternal Infections
  • Antimicrobial Resistance in Staphylococcus
  • Peroxisome Proliferator-Activated Receptors

University of Auckland
2015-2024

Analytical Services
2020

Maurice Wilkins Centre
2009-2019

Medical Research Council
2008

University of Oxford
2008

In Nature, almost every plant is colonized by fungi. Trichoderma virens a biocontrol fungus which has the capacity to behave as an opportunistic endophyte. Even though many plants are this symbiont, exact mechanisms masks its entrance into host remain unknown, but likely involve secretion of different families proteins apoplast that may play crucial roles in suppression immune responses. study, we investigated T. colonization maize roots under hydroponic conditions, evidencing inter- and...

10.3389/fpls.2018.00409 article EN cc-by Frontiers in Plant Science 2018-04-05

Abstract 1‐[(3 S )‐3‐[4‐Amino‐3‐[2‐(3,5‐dimethoxyphenyl)ethynyl]‐1 H ‐pyrazolo[3,4‐ d ]pyrimidin‐1‐yl]‐1‐pyrrolidinyl]‐2‐propen‐1‐one (TAS‐120) is an irreversible inhibitor of the fibroblast growth factor receptor (FGFR) family, and currently under phase I/II clinical trials in patients with confirmed advanced metastatic solid tumours harbouring FGFR aberrations. This specifically targets P‐loop tyrosine kinase domain, forming a covalent adduct cysteine side chain protein. Our mass...

10.1002/cmdc.201800719 article EN ChemMedChem 2019-01-02

Abstract Cofactor F 420 plays critical roles in primary and secondary metabolism a range of bacteria archaea as low-potential hydride transfer agent. It mediates variety important redox transformations involved bacterial persistence, antibiotic biosynthesis, pro-drug activation methanogenesis. However, the biosynthetic pathway for has not been fully elucidated: neither enzyme that generates putative intermediate 2-phospho- l -lactate, nor function FMN-binding C-terminal domain γ-glutamyl...

10.1038/s41467-019-09534-x article EN cc-by Nature Communications 2019-04-05

This study evaluates the effects of alkaline and micellisation extraction methods, alongside freeze-drying spray-drying, on protein subunits, amino acid profiles, proteome data hempseed isolate (HPI). Findings revealed that methods affect profiles more than drying methods. Micellisation-extracted HPI showed higher albumin, oleosin, sulphur-containing levels alkaline-extracted HPI. The alkali-extracted undried sample (AU) gave potentially allergenic proteins, including Hsp70 triosephosphate...

10.1016/j.foodchem.2024.140426 article EN cc-by Food Chemistry 2024-07-17

ABSTRACT The ability to acquire iron from the extracellular environment is a key determinant of pathogenicity in mycobacteria. Mycobacterium tuberculosis acquires exclusively via siderophore mycobactin T, biosynthesis which depends on production salicylate chorismate. Salicylate other bacteria either two-step process involving an isochorismate synthase (chorismate isomerase) and pyruvate lyase, as observed for Pseudomonas aeruginosa , or single-step conversion catalyzed by synthase, with...

10.1128/jb.00338-06 article EN Journal of Bacteriology 2006-08-21

Abstract Hypertension now affects about 600 million people worldwide and is a leading cause of death in the Western world. The spontaneously hypertensive rat (SHR), provides useful model to investigate heart failure (HF). SHR replicates clinical progression hypertension humans, wherein early development followed by long stable period compensated cardiac hypertrophy that slowly progresses HF. Although failing generally shows increased substrate preference towards glucose impaired...

10.1002/pmic.200700977 article EN PROTEOMICS 2008-06-01

In heart failure transverse-tubule (t-tubule) remodelling disrupts calcium release, and contraction. T-tubules in human failing hearts exhibit increased labelling by wheat germ agglutinin (WGA), a lectin that binds to the dystrophin-associated glycoprotein complex. We hypothesized changes this complex may explain WGA contribute t-tubule heart. study we sought identify molecules responsible for labelling.Confocal super-resolution fluorescence microscopy proteomic analyses were used quantify...

10.1093/cvr/cvx055 article EN Cardiovascular Research 2017-03-20

<italic>Mycobacterium tuberculosis</italic> isocitrate lyases (ICLs) form a covalent adduct with itaconate through their catalytic cysteine residue. These results reveal atomic details of inhibition and provide insights into the mechanism ICLs.

10.1039/d0md00301h article EN RSC Medicinal Chemistry 2020-10-19

Abstract Freshwater cyanobacterial blooms have increased worldwide, channeling organic carbon into these systems, and threatening animal health through the production of cyanotoxins. Both toxic nontoxic Microcoleus proliferations usually occur when there are moderate concentrations dissolved inorganic nitrogen, but phosphorus is scarce. In order to understand how establishes thick biofilms (or mats) on riverbeds under phosphorus-limiting conditions, we collected Microcoleus-dominated over a...

10.1038/s41396-020-0676-5 article EN cc-by The ISME Journal 2020-05-18

Cell surface pili are polymeric protein assemblies that enable bacteria to adhere surfaces and specific host tissues. The expressed by Gram-positive constitute a unique paradigm in which sortase-mediated covalent linkages join successive pilin subunits like beads on string. These formed from two or three distinct types of subunit, typically encoded small gene clusters, often with their cognate sortases. In Group A streptococci (GAS), major forms the backbone, whereas minor pilins located at...

10.1074/jbc.m109.089680 article EN cc-by Journal of Biological Chemistry 2010-04-29

Bypass of foregut secreted factors promoting insulin resistance is hypothesized to be one the mechanisms by which resolution type 2 diabetes (T2D) follows roux-en-y gastric bypass (GBP) surgery.To identify resistance-associated proteins and metabolites decrease more after GBP than sleeve gastrectomy (SG) prior remission.Fasting plasma from 15 subjects with T2D undergoing or SG was analyzed proteomic metabolomic methods 3 days before surgery. Subjects were matched for age, BMI, metformin...

10.1371/journal.pone.0096489 article EN cc-by PLoS ONE 2014-05-06

beta-Cell granules contain proteins involved in fuel regulation, which when altered, contribute to metabolic disorders including diabetes mellitus. We analyzed present purified from the INS-1E beta-cell model. Fifty-one component were identified by LC-MS/MS hormones, granins, protein processing components, cellular trafficking enzymes implicated metabolism and chaperone proteins. These findings may increase understanding of granule secretion processes leading aggregation death type-2 diabetes.

10.1021/pr800675k article EN Journal of Proteome Research 2008-12-05

This study aimed to identify new diabetic nephropathy (DN)-related proteins and renal targets of the copper(II)-selective chelator, triethylenetetramine (TETA) in streptozotocin-diabetic rats. We used recently developed iTRAQ technology compare protein profiles among non-diabetic, diabetic, TETA-treated In kidneys, tubulointerstitial nephritis antigen (TINag), voltage-dependent anion-selective channel (VDAC) 1, VDAC2 were up-regulated parallel with alterations expression functions oxidative...

10.1002/pmic.200900285 article EN PROTEOMICS 2009-07-24

Abstract Antimicrobial peptides and proteins represent an important class of plant defensive compounds against pathogens provide a rich source lead in the field drug discovery. We describe effective preparation cysteine‐rich snakin‐1 ‐2 antimicrobial by using combination solid‐phase synthesis native chemical ligation. A subsequent cysteine/cystine mediated oxidative folding to form six internal disulfide bonds concurrently gave folded 40–50 % yield. By comparative evaluation mass...

10.1002/chem.201303207 article EN Chemistry - A European Journal 2014-03-18

The homeostatic chemokine CCL21 has a pivotal role in lymphocyte homing and compartment localisation within the lymph node, also affects adhesion between immune cells. effects of are modulated by its mode presentation, with different cellular responses seen for surface-bound soluble forms. Here we show that plasmin cleaves to release C-terminal peptide responsible binding glycosaminoglycans on extracellular matrix cell surfaces, thereby generating form. Loss this anchoring enabled...

10.1038/icb.2016.56 article EN Immunology and Cell Biology 2016-06-15

Organic micropollutants (OMPs) are pervasive anthropogenic contaminants of receiving waters where they can induce various adverse effects to aquatic life. Their ubiquitous environmental occurrence is primarily attributed discharge from wastewater treatment plants due incomplete removal by common biological processes. Here, we assess a new strategy for promoting the degradation six representative OMPs (i.e., sulfamethoxazole, carbamazepine, tylosin, atrazine, naproxen, and ibuprofen)...

10.1021/acs.est.9b02219 article EN Environmental Science & Technology 2019-07-29

Abstract Poly-γ-glutamate tails are a distinctive feature of archaeal, bacterial, and eukaryotic cofactors, including the folates F 420 . Despite decades research, key mechanistic questions remain as to how enzymes successively add glutamates poly-γ-glutamate chains while maintaining cofactor specificity. Here, we show poly-γ-glutamylation folate by folylpolyglutamate synthases γ-glutamyl ligases, non-homologous enzymes, occurs via processive addition L -glutamate onto growing chain termini....

10.1038/s41467-024-45632-1 article EN cc-by Nature Communications 2024-02-12

Abstract Diabetes now affects more than 5% of the world's population and heart failure is most common cause death amongst diabetic patients. Accumulating evidence supports a view that myocardial mitochondrial structural functional changes are central to onset failure, but exact nature these at proteomic level remains unclear.Here we report on in rat mitochondria following 120 days streptozotocin‐diabetes using recently developed iTRAQ™ labeling method, which permits quantification proteins...

10.1002/prca.200600831 article EN PROTEOMICS - CLINICAL APPLICATIONS 2007-06-01

The Gram-positive organism Corynebacterium diphtheriae, the cause of diphtheria in humans, expresses pili on its surface which it uses for adhesion and colonization host. These are covalent protein polymers composed three types pilin subunit that assembled by specific sortase enzymes. A structural analysis major SpaD, forms polymeric backbone one pilus expressed C. is reported. Mass-spectral crystallographic shows SpaD contains internal Lys-Asn isopeptide bonds. One these, shown mass...

10.1107/s1399004714001400 article EN cc-by Acta Crystallographica Section D Biological Crystallography 2014-04-25

Aberration in FGFR4 signaling drives carcinogenesis and progression a subset of hepatocellular carcinoma (HCC) patients, thereby making an attractive molecular target for this disease. Selective inhibition can be achieved through covalently targeting poorly conserved cysteine residue the kinase domain. We report mass spectrometry assays cocrystal structures covalent complex with clinical candidate BLU554 series four structurally related inhibitors that define inherent reactivity selectivity...

10.1021/acsmedchemlett.9b00196 article EN ACS Medicinal Chemistry Letters 2019-07-03

Abstract Extracellular vesicle (EV) research has grown rapidly in recent years, largely due to the potential use of EVs as liquid biopsy biomarkers or therapeutics. However, in‐depth characterisation and validation produced using conventional vitro cultures can be challenging large area cell monolayers volumes culture media required. To overcome this obstacle, multiple bioreactor designs have been tested for EV production with varying success, but consistency over time these systems not...

10.1002/jex2.60 article EN cc-by-nc Journal of Extracellular Biology 2022-09-01

Biologically active factors produced by the intestine and transported aqueous protein fraction of mesenteric lymph are now thought to contribute significantly development distant organ failure in hemorrhagic shock. Despite likely relevance composition conditioned shock, there is no detailed description its proteome. The aim this study was provide first comprehensive proteome shock-conditioned lymph. Mesenteric collected from 16 male Wistar rats randomized group 1 (n = 8) sham control 2 with...

10.1097/shk.0b013e3181cd8631 article EN Shock 2010-03-23

The chronic inflammatory nature of rhinosinusitis (CRS) makes it a morbid condition for individuals with the disease and one whose pathogenesis is poorly understood. To date, proteomic approaches have been applied successfully in handful CRS studies. In this study we use multifaceted approach, including proteomics (iTRAQ labeling) microbiome (bacterial 16S rRNA gene sequencing) analyses middle meatus swabs, as well immune cell analysis underlying tissue, to investigate host-microbe...

10.3389/fcimb.2017.00504 article EN cc-by Frontiers in Cellular and Infection Microbiology 2017-12-06
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