TY - JOUR
T1 - Structural basis for thermostability and identification of potential active site residues for adenylate kinases from the archaeal genus Methanococcus
AU - Haney, P.
AU - Konisky, J.
AU - Koretke, K. K.
AU - Luthey-Schulten, Z.
AU - Wolynes, P. G.
PY - 1997
Y1 - 1997
N2 - Sequence comparisons of highly related archaeal adenylate kinases (AKs) from the mesophilic Methanococcus voltae, the moderate thermophile Methanococcus thermolithotrophicus, and two extreme thermophiles Methanococcus igneus and Methanococcus jannaschii, allow identification of interactions responsible for the large variation in temperatures for optimal catalytic activity and thermostabilities observed for these proteins. The tertiary structures of the methanococcal AKs have been predicted by using homology modeling to further investigate the potential role of specific interactions on thermal stability and activity. The alignments for the methanococcal AKs have been generated by using an energy-based sequence- structure threading procedure against high-resolution crystal structures of eukaryotic, eubacterial, and mitochondrial adenylate and uridylate (UK) kinases. From these alignments, full atomic model structures have been produced using the program MODELLER. The final structures allow identification of potential active site interactions and place a polyproline region near the active site, both of which are unique to the archaeal AKs. Based on these model structures, the additional polar residues present in the thermophiles could contribute four additional salt bridges and a higher negative surface charge. Since only one of these possible salt bridges is interior, they do not appear significantly to the thermal stability. Instead, our model structures indicate that a larger and moro hydrophobic core, due to a specific increase in aliphatic amino acid content and aliphatic side chain volume, in the thermophilic AKs is responsible for increased thermal stability.
AB - Sequence comparisons of highly related archaeal adenylate kinases (AKs) from the mesophilic Methanococcus voltae, the moderate thermophile Methanococcus thermolithotrophicus, and two extreme thermophiles Methanococcus igneus and Methanococcus jannaschii, allow identification of interactions responsible for the large variation in temperatures for optimal catalytic activity and thermostabilities observed for these proteins. The tertiary structures of the methanococcal AKs have been predicted by using homology modeling to further investigate the potential role of specific interactions on thermal stability and activity. The alignments for the methanococcal AKs have been generated by using an energy-based sequence- structure threading procedure against high-resolution crystal structures of eukaryotic, eubacterial, and mitochondrial adenylate and uridylate (UK) kinases. From these alignments, full atomic model structures have been produced using the program MODELLER. The final structures allow identification of potential active site interactions and place a polyproline region near the active site, both of which are unique to the archaeal AKs. Based on these model structures, the additional polar residues present in the thermophiles could contribute four additional salt bridges and a higher negative surface charge. Since only one of these possible salt bridges is interior, they do not appear significantly to the thermal stability. Instead, our model structures indicate that a larger and moro hydrophobic core, due to a specific increase in aliphatic amino acid content and aliphatic side chain volume, in the thermophilic AKs is responsible for increased thermal stability.
KW - ATP binding
KW - energy function alignment
KW - hydrophobicity
KW - salt bridges
KW - structure prediction
KW - threading
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U2 - 10.1002/(SICI)1097-0134(199705)28:1<117::AID-PROT12>3.0.CO;2-M
DO - 10.1002/(SICI)1097-0134(199705)28:1<117::AID-PROT12>3.0.CO;2-M
M3 - Article
C2 - 9144797
AN - SCOPUS:0030970741
SN - 0887-3585
VL - 28
SP - 117
EP - 130
JO - Proteins: Structure, Function and Bioinformatics
JF - Proteins: Structure, Function and Bioinformatics
IS - 1
ER -