Linked Life Data

16430214

Source:http://linkedlifedata.com/resource/pubmed/id/16430214

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2006-1-24
pubmed:databankReference
pubmed:abstractText
The HAD superfamily is a large superfamily of proteins which share a conserved core domain that provides those active site residues responsible for the chemistry common to all family members. The superfamily is further divided into the four subfamilies I, IIA, IIB, and III, based on the topology and insertion site of a cap domain that provides substrate specificity. This structural and functional division implies that members of a given HAD structural subclass may target substrates that have similar structural characteristics. To understand the structure/function relationships in all of the subfamilies, a type IIA subfamily member, NagD from Escherichia coli K-12, was selected (type I, IIB, and III members have been more extensively studied). The structure of the NagD protein was solved to 1.80 A with R(work) = 19.8% and R(free) = 21.8%. Substrate screening and kinetic analysis showed NagD to have high specificity for nucleotide monophosphates with k(cat)/K(m) = 3.12 x 10(4) and 1.28 x 10(4) microM(-)(1) s(-)(1) for UMP and GMP, respectively. This specificity is consistent with the presence of analogues of NagD that exist as fusion proteins with a nucleotide pyrophosphatase from the Nudix family. Docking of the nucleoside substrate in the active site brings it in contact with conserved residues from the cap domain that can act as a substrate specificity loop (NagD residues 144-149) in the type IIA subfamily. NagD and other subfamily IIA and IIB members show the common trait that substrate specificity and catalytic efficiencies (k(cat)/K(m)) are low (1 x 10(4) M(-)(1) s(-)(1)) and the boundaries defining physiological substrates are somewhat overlapping. The ability to catabolize other related secondary metabolites indicates that there is regulation at the genetic level.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0006-2960
pubmed:author
pubmed:issnType
Print
pubmed:day
31
pubmed:volume
45
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1183-93
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed-meshheading:16430214-Aldose-Ketose Isomerases, pubmed-meshheading:16430214-Catalysis, pubmed-meshheading:16430214-Cloning, Molecular, pubmed-meshheading:16430214-Computational Biology, pubmed-meshheading:16430214-Crystallization, pubmed-meshheading:16430214-Crystallography, X-Ray, pubmed-meshheading:16430214-Escherichia coli, pubmed-meshheading:16430214-Escherichia coli Proteins, pubmed-meshheading:16430214-Evolution, Molecular, pubmed-meshheading:16430214-Hydrolases, pubmed-meshheading:16430214-Hydrolysis, pubmed-meshheading:16430214-Kinetics, pubmed-meshheading:16430214-Models, Biological, pubmed-meshheading:16430214-Nucleotidases, pubmed-meshheading:16430214-Phosphoric Acid Esters, pubmed-meshheading:16430214-Protein Conformation, pubmed-meshheading:16430214-Structure-Activity Relationship, pubmed-meshheading:16430214-Substrate Specificity
pubmed:year
2006
pubmed:articleTitle
Structure and activity analyses of Escherichia coli K-12 NagD provide insight into the evolution of biochemical function in the haloalkanoic acid dehalogenase superfamily.
pubmed:affiliation
Department of Physiology and Biophysics, Boston University School of Medicine, Boston, Massachusetts 02118-2394, USA.
pubmed:publicationType
Journal Article, Research Support, N.I.H., Extramural