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Structural plasticity of thermophilic serine hydroxymethyltransferases
Author(s) -
Paiardini Alessandro,
Gianese Giulio,
Bossa Francesco,
Pascarella Stefano
Publication year - 2002
Publication title -
proteins: structure, function, and bioinformatics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.699
H-Index - 191
eISSN - 1097-0134
pISSN - 0887-3585
DOI - 10.1002/prot.10268
Subject(s) - thermophile , serine hydroxymethyltransferase , extremophile , thermostability , thermolabile , mesophile , thermus thermophilus , biochemistry , serine , amino acid , chemistry , protein superfamily , extreme environment , biology , homology (biology) , enzyme , genetics , gene , escherichia coli , bacteria
Serine hydroxymethyltransferase (SHMT) catalyzes the reversible cleavage of serine to form glycine and monocarbonic groups, essential in several biosynthetic pathways. The availability of crystallographic structures of SHMT from mesophilic organisms and information produced by the genomic projects prompted the analysis of the adaptation of SHMT to “extreme” environments, such as high temperatures, by exploitation of structural data from thermophilic organisms. The sequences of 10 thermophilic/hyperthermophilic SHMTs were multiply aligned to 53 mesophilic homologs and analyzed by a comparative approach, examining the amino acid compositions and preferred residue exchanges between mesophiles and extremophiles. The structural basis of the observed exchanges was further investigated through the application of homology modeling to the 10 extremophilic SHMTs. The results of this study indicate that, in SHMT, thermal stability can be achieved mainly through three strategies: (i) increased number of charged residues at the protein surface; (ii) increased hydrophobicity of the protein core; and (iii) substitution of thermolabile residues exposed to the solvent. Additional features of the archaeal SHMTs, for which no structural data are available yet, were also investigated to explain their quaternary assemblage and the interaction with modified folates. Proteins 2003;50:122–134. © 2002 Wiley‐Liss, Inc.