J Michael Sauder - Target selection and annotation for the structural genomics of the amidohydrolase and enolase superfamilies

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  Publication Details (including relevant citation   information):

  J Struct Funct Genomics (2009) 10: 107-125.

  Pieper U, Chiang R, Seffernick JJ, Brown SD, Glasner ME, Kelly L,   Eswar N, Sauder JM, Bonanno JB, Swaminathan S, Burley SK, Zheng   X, Chance MR, Almo SC, Gerlt JA, Raushel FM, Jacobson MP, Babbitt   PC, Sali A


  To study the substrate specificity of enzymes, we use the   amidohydrolase  and enolase superfamilies as model systems;   members of these  superfamilies share a common TIM barrel   fold and catalyze a wide range  of chemical reactions. Here,   we describe a collaboration between the  Enzyme Specificity   Consortium (ENSPEC) and the New York SGX Research  Center   for Structural Genomics (NYSGXRC) that aims to maximize the    structural coverage of the amidohydrolase and enolase   superfamilies.  Using sequence- and structure-based protein   comparisons, we first  selected 535 target proteins from a   variety of genomes for  high-throughput structure   determination by X-ray crystallography; 63 of  these targets   were not previously annotated as superfamily members. To    date, 20 unique amidohydrolase and 41 unique enolase structures   have  been determined, increasing the fraction of sequences   in the two  superfamilies that can be modeled based on at   least 30% sequence  identity from 45% to 73%. We present   case studies of proteins related to  uronate isomerase (an   amidohydrolase superfamily member) and mandelate  racemase   (an enolase superfamily member), to illustrate how this    structure-focused approach can be used to generate hypotheses   about  sequence-structure-function relationships.

  Address (URL): http://www.ncbi.nlm.nih.gov/pubmed/19219566