2iy0

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SENP1 (mutant) SUMO1 RanGAPSENP1 (mutant) SUMO1 RanGAP

Structural highlights

2iy0 is a 3 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 2.77Å
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

SENP1_HUMAN Protease that catalyzes two essential functions in the SUMO pathway: processing of full-length SUMO1, SUMO2 and SUMO3 to their mature forms and deconjugation of SUMO1, SUMO2 and SUMO3 from targeted proteins. Deconjugates SUMO1 from HIPK2. Deconjugates SUMO1 from HDAC1, which decreases its transcriptional repression activity.[1] [2] [3] [4]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

Small ubiquitin-like modifier (SUMO)-specific protease SENP1 processes SUMO-1, SUMO-2 and SUMO-3 to mature forms and deconjugates them from modified proteins. To establish the proteolytic mechanism, we determined structures of catalytically inactive SENP1 bound to SUMO-1-modified RanGAP1 and to unprocessed SUMO-1. In each case, the scissile peptide bond is kinked at a right angle to the C-terminal tail of SUMO-1 and has the cis configuration of the amide nitrogens. SENP1 preferentially processes SUMO-1 over SUMO-2, but binding thermodynamics of full-length SUMO-1 and SUMO-2 to SENP1 and K(m) values for processing are very similar. However, k(cat) values differ by 50-fold. Thus, discrimination between unprocessed SUMO-1 and SUMO-2 by SENP1 is based on a catalytic step rather than substrate binding and is likely to reflect differences in the ability of SENP1 to correctly orientate the scissile bonds in SUMO-1 and SUMO-2.

SUMO protease SENP1 induces isomerization of the scissile peptide bond.,Shen L, Tatham MH, Dong C, Zagorska A, Naismith JH, Hay RT Nat Struct Mol Biol. 2006 Dec;13(12):1069-77. Epub 2006 Nov 12. PMID:17099698[5]

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

See Also

References

  1. Gong L, Millas S, Maul GG, Yeh ET. Differential regulation of sentrinized proteins by a novel sentrin-specific protease. J Biol Chem. 2000 Feb 4;275(5):3355-9. PMID:10652325
  2. Cheng J, Wang D, Wang Z, Yeh ET. SENP1 enhances androgen receptor-dependent transcription through desumoylation of histone deacetylase 1. Mol Cell Biol. 2004 Jul;24(13):6021-8. PMID:15199155 doi:10.1128/MCB.24.13.6021-6028.2004
  3. Kim YH, Sung KS, Lee SJ, Kim YO, Choi CY, Kim Y. Desumoylation of homeodomain-interacting protein kinase 2 (HIPK2) through the cytoplasmic-nuclear shuttling of the SUMO-specific protease SENP1. FEBS Lett. 2005 Nov 7;579(27):6272-8. Epub 2005 Oct 19. PMID:16253240 doi:S0014-5793(05)01251-2
  4. Shen LN, Dong C, Liu H, Naismith JH, Hay RT. The structure of SENP1-SUMO-2 complex suggests a structural basis for discrimination between SUMO paralogues during processing. Biochem J. 2006 Jul 15;397(2):279-88. PMID:16553580 doi:10.1042/BJ20052030
  5. Shen L, Tatham MH, Dong C, Zagorska A, Naismith JH, Hay RT. SUMO protease SENP1 induces isomerization of the scissile peptide bond. Nat Struct Mol Biol. 2006 Dec;13(12):1069-77. Epub 2006 Nov 12. PMID:17099698 doi:10.1038/nsmb1172

2iy0, resolution 2.77Å

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