TY - JOUR
T1 - Target selection and annotation for the structural genomics of the amidohydrolase and enolase superfamilies
AU - Pieper, Ursula
AU - Chiang, Ranyee
AU - Seffernick, Jennifer J.
AU - Brown, Shoshana D.
AU - Glasner, Margaret E.
AU - Kelly, Libusha
AU - Eswar, Narayanan
AU - Sauder, J. Michael
AU - Bonanno, Jeffrey B.
AU - Swaminathan, Subramanyam
AU - Burley, Stephen K.
AU - Zheng, Xiaojing
AU - Chance, Mark R.
AU - Almo, Steven C.
AU - Gerlt, John A.
AU - Raushel, Frank M.
AU - Jacobson, Matthew P.
AU - Babbitt, Patricia C.
AU - Sali, Andrej
PY - 2009/4
Y1 - 2009/4
N2 - 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.
AB - 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.
KW - Amidohydrolase and enolase superfamilies
KW - Structural genomics
KW - Structure annotation
KW - Target selection
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U2 - 10.1007/s10969-008-9056-5
DO - 10.1007/s10969-008-9056-5
M3 - Article
C2 - 19219566
AN - SCOPUS:62949220795
SN - 1345-711X
VL - 10
SP - 107
EP - 125
JO - Journal of Structural and Functional Genomics
JF - Journal of Structural and Functional Genomics
IS - 2
ER -