TY - GEN
T1 - In-silico prediction of surface residue clusters for enzyme-substrate specificity
AU - Yu, Gong Xin
AU - Park, Byung Hoon
AU - Chandramohan, Praveen
AU - Geist, Al
AU - Samatova, Nagiza F.
PY - 2004
Y1 - 2004
N2 - One of the most remarkable properties of enzyme-substrate binding is the high substrate specificity among homologous enzymes. Identification of regions in enzymes that play an important role in substrate recognition presents an opportunity to understand their basic molecular mechanisms. Current methods are limited to identifying conserved residues, ignoring potential contributions of non-conserved residues. Our method overcomes this limitation. In case studies, we investigated several highly homologous enzymatic protein pairs such as guanylyl vs. adenylyl cyclases and lactate vs. malate dehydrogenases, and applied our method on plant and cyano-bacterial RuBisCos. We identified several critical mono-residue and multi-residue clusters that were consistent with experimental results. Some of the identified clusters, primarily the mono-residue ones, represent residues that are directly involved in enzyme-substrate interactions. Others, mostly the multi-residue ones, represent residues vital for domain-domain and regulator-enzyme interactions, indicating their complementary roles in specificity determination.
AB - One of the most remarkable properties of enzyme-substrate binding is the high substrate specificity among homologous enzymes. Identification of regions in enzymes that play an important role in substrate recognition presents an opportunity to understand their basic molecular mechanisms. Current methods are limited to identifying conserved residues, ignoring potential contributions of non-conserved residues. Our method overcomes this limitation. In case studies, we investigated several highly homologous enzymatic protein pairs such as guanylyl vs. adenylyl cyclases and lactate vs. malate dehydrogenases, and applied our method on plant and cyano-bacterial RuBisCos. We identified several critical mono-residue and multi-residue clusters that were consistent with experimental results. Some of the identified clusters, primarily the mono-residue ones, represent residues that are directly involved in enzyme-substrate interactions. Others, mostly the multi-residue ones, represent residues vital for domain-domain and regulator-enzyme interactions, indicating their complementary roles in specificity determination.
UR - http://www.scopus.com/inward/record.url?scp=14044259349&partnerID=8YFLogxK
M3 - Conference contribution
AN - SCOPUS:14044259349
SN - 0769521940
SN - 9780769521947
T3 - Proceedings - 2004 IEEE Computational Systems Bioinformatics Conference, CSB 2004
SP - 696
EP - 697
BT - Proceedings - 2004 IEEE Computational Systems Bioinformatics Conference, CSB 2004
T2 - Proceedings - 2004 IEEE Computational Systems Bioinformatics Conference, CSB 2004
Y2 - 16 August 2004 through 19 August 2004
ER -