Linked Life Data

11841211

Source:http://linkedlifedata.com/resource/pubmed/id/11841211

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
7
pubmed:dateCreated
2002-2-13
pubmed:databankReference
pubmed:abstractText
Aminodeoxychorismate synthase is part of a heterodimeric complex that catalyzes the two-step biosynthesis of 4-amino-4-deoxychorismate, a precursor of p-aminobenzoate and folate in microorganisms. In the first step, a glutamine amidotransferase encoded by the pabA gene generates ammonia as a substrate that, along with chorismate, is used in the second step, catalyzed by aminodeoxychorismate synthase, the product of the pabB gene. Here we report the X-ray crystal structure of Escherichia coli PabB determined in two different crystal forms, each at 2.0 A resolution. The 453-residue monomeric PabB has a complex alpha/beta fold which is similar to that seen in the structures of homologous, oligomeric TrpE subunits of several anthranilate synthases of microbial origin. A comparison of the structures of these two classes of chorismate-utilizing enzymes provides a rationale for the differences in quaternary structures seen for these enzymes, and indicates that the weak or transient association of PabB with PabA during catalysis stems at least partly from a limited interface for protein interactions. Additional analyses of the structures enabled the tentative identification of the active site of PabB, which contains a number of residues implicated from previous biochemical and genetic studies to be essential for activity. Differences in the structures determined from phosphate- and formate-grown crystals, and the location of an adventitious formate ion, suggest that conformational changes in loop regions adjacent to the active site may be needed for catalysis. A surprising finding in the structure of PabB was the presence of a tryptophan molecule deeply embedded in a binding pocket that is analogous to the regulatory site in the TrpE subunits of the anthranilate synthases. The strongly bound ligand, which cannot be dissociated without denaturation of PabB, may play a structural role in the enzyme since there is no effect of tryptophan on the enzymic synthesis of aminodeoxychorismate. Extensive sequence similarity in the tryptophan-binding pocket among several other chorismate-utilizing enzymes, including isochorismate synthase, suggests that they too may bind tryptophan for structural integrity, and corroborates early ideas on the evolution of this interesting enzyme family.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0006-2960
pubmed:author
pubmed:issnType
Print
pubmed:day
19
pubmed:volume
41
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2198-208
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:11841211-Amino Acid Sequence, pubmed-meshheading:11841211-Binding Sites, pubmed-meshheading:11841211-Carbon-Nitrogen Ligases, pubmed-meshheading:11841211-Chorismic Acid, pubmed-meshheading:11841211-Conserved Sequence, pubmed-meshheading:11841211-Crystallization, pubmed-meshheading:11841211-Crystallography, X-Ray, pubmed-meshheading:11841211-Escherichia coli, pubmed-meshheading:11841211-Evolution, Molecular, pubmed-meshheading:11841211-Models, Molecular, pubmed-meshheading:11841211-Molecular Sequence Data, pubmed-meshheading:11841211-Protein Structure, Secondary, pubmed-meshheading:11841211-Sequence Alignment, pubmed-meshheading:11841211-Sequence Homology, Amino Acid, pubmed-meshheading:11841211-Structure-Activity Relationship, pubmed-meshheading:11841211-Transaminases, pubmed-meshheading:11841211-Tryptophan
pubmed:year
2002
pubmed:articleTitle
Structure of Escherichia coli aminodeoxychorismate synthase: architectural conservation and diversity in chorismate-utilizing enzymes.
pubmed:affiliation
Center for Advanced Research in Biotechnology, University of Maryland Biotechnology Institute, National Institute of Standards and Technology, 9600 Gudelsky Drive, Rockville, Maryland 20850, USA.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, U.S. Gov't, Non-P.H.S.