Martin AC

References (4)

Title : Exploitation of a Novel Binding Pocket in Human Lipoprotein-Associated Phospholipase A2 (Lp-PLA2) Discovered through X-ray Fragment Screening - Woolford_2016_J.Med.Chem_59_5356
Author(s) : Woolford AJ , Pero JE , Aravapalli S , Berdini V , Coyle JE , Day PJ , Dodson AM , Grondin P , Holding FP , Lee LY , Li P , Manas ES , Marino J, Jr. , Martin AC , McCleland BW , McMenamin RL , Murray CW , Neipp CE , Page LW , Patel VK , Potvain F , Rich S , Rivero RA , Smith K , Somers DO , Trottet L , Velagaleti R , Williams G , Xie R
Ref : Journal of Medicinal Chemistry , 59 :5356 , 2016
Abstract : Elevated levels of human lipoprotein-associated phospholipase A2 (Lp-PLA2) are associated with cardiovascular disease and dementia. A fragment screen was conducted against Lp-PLA2 in order to identify novel inhibitors. Multiple fragment hits were observed in different regions of the active site, including some hits that bound in a pocket created by movement of a protein side chain (approximately 13 A from the catalytic residue Ser273). Using structure guided design, we optimized a fragment that bound in this pocket to generate a novel low nanomolar chemotype, which did not interact with the catalytic residues.
ESTHER : Woolford_2016_J.Med.Chem_59_5356
PubMedSearch : Woolford_2016_J.Med.Chem_59_5356
PubMedID: 27167608
Gene_locus related to this paper: human-PLA2G7

Title : Lipoprotein lipase deficiency presenting with neonatal perianal abscesses - Akesson_2016_BMJ.Case.Rep_2016_
Author(s) : Akesson LS , Burnett JR , Mehta DK , Martin AC
Ref : BMJ Case Rep , 2016 : , 2016
Abstract : Lipoprotein lipase (LPL), a member of the triglyceride lipase gene family, is synthesised by parenchymal cells of the heart, skeletal muscle and adipose tissues before being transported to luminal surfaces of vascular endothelial cells to exert its main physiological function to hydrolyse plasma lipoproteins. LPL deficiency is a rare autosomal recessive disorder, resulting in severe hypertriglyceridaemia from birth. The effect of marked hypertriglyceridaemia on the immune function in children has not been described. We present a case of a neonate with LPL deficiency and grossly elevated plasma triglyceride levels, presenting with recurrent and recalcitrant perianal abscesses suggestive of underlying immunodeficiency. With reduced levels of plasma triglycerides, the recurrent perianal infections resolved. This case report reviews evidence for potential deleterious effects of hypertriglyceridaemia on immune function, however, underlying mechanisms are poorly understood. Whether hypertriglyceridaemia contributes to immune dysfunction in this context is unknown. If there is a pathophysiological link, this may have implications for hypertriglyceridaemia management.
ESTHER : Akesson_2016_BMJ.Case.Rep_2016_
PubMedSearch : Akesson_2016_BMJ.Case.Rep_2016_
PubMedID: 26825936

Title : Using the CATH domain database to assign structures and functions to the genome sequences - Pearl_2000_Biochem.Soc.Trans_28_269
Author(s) : Pearl F , Todd AE , Bray JE , Martin AC , Salamov AA , Suwa M , Swindells MB , Thornton JM , Orengo CA
Ref : Biochemical Society Transactions , 28 :269 , 2000
Abstract : The CATH database of protein structures contains approximately 18000 domains organized according to their (C)lass, (A)rchitecture, (T)opology and (H)omologous superfamily. Relationships between evolutionary related structures (homologues) within the database have been used to test the sensitivity of various sequence search methods in order to identify relatives in Genbank and other sequence databases. Subsequent application of the most sensitive and efficient algorithms, gapped blast and the profile based method, Position Specific Iterated Basic Local Alignment Tool (PSI-BLAST), could be used to assign structural data to between 22 and 36 % of microbial genomes in order to improve functional annotation and enhance understanding of biological mechanism. However, on a cautionary note, an analysis of functional conservation within fold groups and homologous superfamilies in the CATH database, revealed that whilst function was conserved in nearly 55% of enzyme families, function had diverged considerably, in some highly populated families. In these families, functional properties should be inherited far more cautiously and the probable effects of substitutions in key functional residues carefully assessed.
ESTHER : Pearl_2000_Biochem.Soc.Trans_28_269
PubMedSearch : Pearl_2000_Biochem.Soc.Trans_28_269
PubMedID: 10816141

Title : The CATH Database provides insights into protein structure\/function relationships - Orengo_1999_Nucleic.Acids.Res_27_275
Author(s) : Orengo CA , Pearl FM , Bray JE , Todd AE , Martin AC , Lo Conte L , Thornton JM
Ref : Nucleic Acids Research , 27 :275 , 1999
Abstract : We report the latest release (version 1.4) of the CATH protein domains database ( This is a hierarchical classification of 13 359 protein domain structures into evolutionary families and structural groupings. We currently identify 827 homologous families in which the proteins have both structual similarity and sequence and/or functional similarity. These can be further clustered into 593 fold groups and 32 distinct architectures. Using our structural classification and associated data on protein functions, stored in the database (EC identifiers, SWISS-PROT keywords and information from the Enzyme database and literature) we have been able to analyse the correlation between the 3D structure and function. More than 96% of folds in the PDB are associated with a single homologous family. However, within the superfolds, three or more different functions are observed. Considering enzyme functions, more than 95% of clearly homologous families exhibit either single or closely related functions, as demonstrated by the EC identifiers of their relatives. Our analysis supports the view that determining structures, for example as part of a 'structural genomics' initiative, will make a major contribution to interpreting genome data.
ESTHER : Orengo_1999_Nucleic.Acids.Res_27_275
PubMedSearch : Orengo_1999_Nucleic.Acids.Res_27_275
PubMedID: 9847200