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Conformational transitions driven by pyridoxal-5'-phosphate uptake in the psychrophilic serine hydroxymethyltransferase from Psychromonas ingrahamii.
Proteins. 2014 Oct; 82(10):2831-41.P

Abstract

Serine hydroxymethyltransferase (SHMT) is a pyridoxal-5'-phosphate (PLP)-dependent enzyme belonging to the fold type I superfamily, which catalyzes in vivo the reversible conversion of l-serine and tetrahydropteroylglutamate (H₄PteGlu) to glycine and 5,10-methylenetetrahydropteroylglutamate (5,10-CH₂-H₄PteGlu). The SHMT from the psychrophilic bacterium Psychromonas ingrahamii (piSHMT) had been recently purified and characterized. This enzyme was shown to display catalytic and stability properties typical of psychrophilic enzymes, namely high catalytic activity at low temperature and thermolability. To gain deeper insights into the structure-function relationship of piSHMT, the three-dimensional structure of its apo form was determined by X-ray crystallography. Homology modeling techniques were applied to build a model of the piSHMT holo form. Comparison of the two forms unraveled the conformation modifications that take place when the apo enzyme binds its cofactor. Our results show that the apo form is in an "open" conformation and possesses four (or five, in chain A) disordered loops whose electron density is not visible by X-ray crystallography. These loops contain residues that interact with the PLP cofactor and three of them are localized in the major domain that, along with the small domain, constitutes the single subunit of the SHMT homodimer. Cofactor binding triggers a rearrangement of the small domain that moves toward the large domain and screens the PLP binding site at the solvent side. Comparison to the mesophilic apo SHMT from Salmonella typhimurium suggests that the backbone conformational changes are wider in psychrophilic SHMT.

Authors+Show Affiliations

Dipartimento di Scienze Biochimiche "A. Rossi Fanelli", Università La Sapienza, 00185, Roma, Italy.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

25044250

Citation

Angelaccio, Sebastiana, et al. "Conformational Transitions Driven By Pyridoxal-5'-phosphate Uptake in the Psychrophilic Serine Hydroxymethyltransferase From Psychromonas Ingrahamii." Proteins, vol. 82, no. 10, 2014, pp. 2831-41.
Angelaccio S, Dworkowski F, Di Bello A, et al. Conformational transitions driven by pyridoxal-5'-phosphate uptake in the psychrophilic serine hydroxymethyltransferase from Psychromonas ingrahamii. Proteins. 2014;82(10):2831-41.
Angelaccio, S., Dworkowski, F., Di Bello, A., Milano, T., Capitani, G., & Pascarella, S. (2014). Conformational transitions driven by pyridoxal-5'-phosphate uptake in the psychrophilic serine hydroxymethyltransferase from Psychromonas ingrahamii. Proteins, 82(10), 2831-41. https://doi.org/10.1002/prot.24646
Angelaccio S, et al. Conformational Transitions Driven By Pyridoxal-5'-phosphate Uptake in the Psychrophilic Serine Hydroxymethyltransferase From Psychromonas Ingrahamii. Proteins. 2014;82(10):2831-41. PubMed PMID: 25044250.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Conformational transitions driven by pyridoxal-5'-phosphate uptake in the psychrophilic serine hydroxymethyltransferase from Psychromonas ingrahamii. AU - Angelaccio,Sebastiana, AU - Dworkowski,Florian, AU - Di Bello,Angela, AU - Milano,Teresa, AU - Capitani,Guido, AU - Pascarella,Stefano, Y1 - 2014/08/05/ PY - 2014/03/16/received PY - 2014/06/19/revised PY - 2014/07/03/accepted PY - 2014/7/22/entrez PY - 2014/7/22/pubmed PY - 2015/10/28/medline KW - B' factors KW - X-ray crystallography KW - apo enzyme KW - conformational transition KW - flexibility KW - holo enzyme KW - homology modeling KW - psychrophilic enzyme KW - pyridoxal-5′-phosphate KW - serine hydroxymethyltransferase SP - 2831 EP - 41 JF - Proteins JO - Proteins VL - 82 IS - 10 N2 - Serine hydroxymethyltransferase (SHMT) is a pyridoxal-5'-phosphate (PLP)-dependent enzyme belonging to the fold type I superfamily, which catalyzes in vivo the reversible conversion of l-serine and tetrahydropteroylglutamate (H₄PteGlu) to glycine and 5,10-methylenetetrahydropteroylglutamate (5,10-CH₂-H₄PteGlu). The SHMT from the psychrophilic bacterium Psychromonas ingrahamii (piSHMT) had been recently purified and characterized. This enzyme was shown to display catalytic and stability properties typical of psychrophilic enzymes, namely high catalytic activity at low temperature and thermolability. To gain deeper insights into the structure-function relationship of piSHMT, the three-dimensional structure of its apo form was determined by X-ray crystallography. Homology modeling techniques were applied to build a model of the piSHMT holo form. Comparison of the two forms unraveled the conformation modifications that take place when the apo enzyme binds its cofactor. Our results show that the apo form is in an "open" conformation and possesses four (or five, in chain A) disordered loops whose electron density is not visible by X-ray crystallography. These loops contain residues that interact with the PLP cofactor and three of them are localized in the major domain that, along with the small domain, constitutes the single subunit of the SHMT homodimer. Cofactor binding triggers a rearrangement of the small domain that moves toward the large domain and screens the PLP binding site at the solvent side. Comparison to the mesophilic apo SHMT from Salmonella typhimurium suggests that the backbone conformational changes are wider in psychrophilic SHMT. SN - 1097-0134 UR - https://www.unboundmedicine.com/medline/citation/25044250/Conformational_transitions_driven_by_pyridoxal_5'_phosphate_uptake_in_the_psychrophilic_serine_hydroxymethyltransferase_from_Psychromonas_ingrahamii_ L2 - https://doi.org/10.1002/prot.24646 DB - PRIME DP - Unbound Medicine ER -