5cbp

From Proteopedia

Jump to: navigation, search

Crystal Structure of Conjoint Pyrococcus furiosus L-asparaginase at 37 degree C

Structural highlights

5cbp is a 2 chain structure with sequence from Pyrococcus furiosus DSM 3638. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 2.358Å
Ligands:FLC, GOL, IPA
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

ASPG_PYRFU Catalyzes the hydrolysis of L-asparagine into L-aspartate and ammonia. Displays no glutaminase activity, a highly desirable therapeutic property.[1] [2]

Publication Abstract from PubMed

It remains undeciphered how thermophilic enzymes display enhanced stability at elevated temperatures. Taking L-asparaginase from P. furiosus (PfA) as an example, we combined scattering shapes deduced from small-angle X-ray scattering (SAXS) data at increased temperatures with symmetry mates from crystallographic structures to find that heating caused end-to-end association. The small contact point of self-binding appeared to be enabled by a terminal short beta-strand in N-terminal domain, Leu(179)-Val-Val-Asn(182) (LVVN). Interestingly, deletion of this strand led to a defunct enzyme, whereas suplementation of the peptide LVVN to the defunct enzyme restored structural frameworkwith mesophile-type functionality. Crystal structure of the peptide-bound defunct enzyme showed that one peptide ispresent in the same coordinates as in original enzyme, explaining gain-of lost function. A second peptide was seen bound to the protein at a different location suggesting its possible role in substrate-free molecular-association. Overall, we show that the heating induced self-assembly of native shapes of PfA led to an apparent super-stable assembly.

Heat induces end to end repetitive association in P. furiosus L-asparaginase which enables its thermophilic property.,Sharma P, Tomar R, Yadav SS, Badmalia MD, Nath SK, Ashish, Kundu B Sci Rep. 2020 Dec 10;10(1):21702. doi: 10.1038/s41598-020-78877-z. PMID:33303914[3]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

Loading citation details..
Citations
1 reviews cite this structure
Thermo-L-Asparaginases: From the Role in the Viability of Thermophiles and Hyperthermophiles at High Temperatures to a Molecular Understanding of Their Thermoactivity and Thermostability.
Dumina et al. (2023)
0 more
1 other articles
No citations found

See Also

References

  1. ↑ Bansal S, Gnaneswari D, Mishra P, Kundu B. Structural stability and functional analysis of L-asparaginase from Pyrococcus furiosus. Biochemistry (Mosc). 2010 Mar;75(3):375-81. doi: 10.1134/s0006297910030144. PMID:20370616 doi:http://dx.doi.org/10.1134/s0006297910030144
  2. ↑ Bansal S, Srivastava A, Mukherjee G, Pandey R, Verma AK, Mishra P, Kundu B. Hyperthermophilic asparaginase mutants with enhanced substrate affinity and antineoplastic activity: structural insights on their mechanism of action. FASEB J. 2012 Mar;26(3):1161-71. doi: 10.1096/fj.11-191254. Epub 2011 Dec 13. PMID:22166247 doi:http://dx.doi.org/10.1096/fj.11-191254
  3. ↑ Sharma P, Tomar R, Yadav SS, Badmalia MD, Nath SK, Ashish, Kundu B. Heat induces end to end repetitive association in P. furiosus L-asparaginase which enables its thermophilic property. Sci Rep. 2020 Dec 10;10(1):21702. doi: 10.1038/s41598-020-78877-z. PMID:33303914 doi:http://dx.doi.org/10.1038/s41598-020-78877-z

Contents


PDB ID 5cbp

Drag the structure with the mouse to rotate

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://proteopedia.org/wiki/index.php/5cbp"
Personal tools