title: Conserved water molecules in bacterial serine hydroxymethyltransferases.
abstract: Water molecules occurring in the interior of protein structures often are endowed with key structural and functional roles. We report the results of a systematic analysis of conserved water molecules in bacterial serine hydroxymethyltransferases (SHMTs). SHMTs are an important group of pyridoxal-5'-phosphate-dependent enzymes that catalyze the reversible conversion of l-serine and tetrahydropteroylglutamate to glycine and 5,10-methylenetetrahydropteroylglutamate. The approach utilized in this study relies on two programs, ProACT2 and WatCH. The first software is able to categorize water molecules in a protein crystallographic structure as buried, positioned in clefts or at the surface. The other program finds, in a set of superposed homologous proteins, water molecules that occur approximately in equivalent position in each of the considered structures. These groups of molecules are referred to as 'clusters' and represent structurally conserved water molecules. Several conserved clusters of buried or cleft water molecules were found in the set of 11 bacterial SHMTs we took into account for this work. The majority of these clusters were not described previously. Possible structural and functional roles for the conserved water molecules are envisaged. This work provides a map of the conserved water molecules helpful for deciphering SHMT mechanism and for rational design of molecular engineering experiments.
authors.affiliation: Dipartimento di Scienze Biochimiche 'A. Rossi Fanelli', Università La Sapienza, Roma 00185, Italy.
authors.forename: Teresa
authors.initials: T
authors.lastname: Milano
authors.affiliation: Dipartimento di Scienze Biochimiche 'A. Rossi Fanelli', Università La Sapienza, Roma 00185, Italy.
authors.forename: Martino Luigi
authors.initials: ML
authors.lastname: Di Salvo
authors.affiliation: Dipartimento di Scienze Biochimiche 'A. Rossi Fanelli', Università La Sapienza, Roma 00185, Italy.
authors.forename: Sebastiana
authors.initials: S
authors.lastname: Angelaccio
authors.affiliation: Dipartimento di Scienze Biochimiche 'A. Rossi Fanelli', Università La Sapienza, Roma 00185, Italy stefano.pascarella@uniroma1.it.
authors.forename: Stefano
authors.initials: S
authors.lastname: Pascarella
mesh_terms: D001419:Bacteria / Q000201:enzymology*; D017124:Conserved Sequence; D012696:Glycine Hydroxymethyltransferase / Q000737:chemistry*; D056004:Molecular Dynamics Simulation; D011487:Protein Conformation; D014867:Water
chemical_list: D014867:Water; D012696:Glycine Hydroxymethyltransferase
keywords: buried and cleft water; conserved water molecules; molecular dynamics; pyridoxal 5′-phosphate; serine hydroxymethyltransferase