NMR solution structure of Thermotoga maritima protein TM1509 reveals a Zn-metalloprotease-like tertiary structure

  • Catherine Hervé du Penhoat
  • Zhaohui Li
  • Hanudatta S. Atreya
  • Seho Kim
  • Adelinda Yee
  • Rong Xiao
  • Diana Murray
  • Cheryl H. Arrowsmith
  • Thomas Szyperski
Article

Abstract

The 150-residue protein TM1509 is encoded in gene YF09_THEMA of Thermotoga maritima. TM1509 has so far no functional annotation and belongs to protein family UPF0054 (PFAM accession number: PF02130) which contains at least 146 members. The NMR structure of TM1509 reveals an α+β fold comprising a four stranded β-sheet with topology A(↑), B(↑), D(↑), C(↓) as well as five α-helices I–V. The structures of most members of family PF02130 can be reliably constructed using the TM1509 NMR structure, demonstrating high leverage for exploration of fold space. A multiple sequence alignment of TM1509 with homologues of family UPF0054 shows that three polypeptide segments, as well as a putative zinc-binding consensus motif HGXLHLXGYDH located at the C-terminal end of α-helix IV, are highly conserved. The spatial arrangement of the three His residues of this UPF0054 consensus motif is similar to the arrangement found for the His residues in the HEXXHXXGXXH zinc-binding consensus motif of matrix metallo-proteases (MMPs). Moreover, the other conserved polypeptide segments form a large cavity which encloses the putative Zn-binding pocket and might confer specificity during catalysis. However, TM1509 and the other members of the UPF0054 family do not have the crucial Glu residue in position 2 of the MMP consensus motif. Intriguingly, the TM1509 structure indicates that the Asp in the UPF0054 consensus motif (Asp 111 in TM1509) may overtake the catalytic role of the Glu. This suggests that protein family UPF0054 might contain members of a hitherto uncharacterized class of metalloproteases.

Keywords

matrix metalloproteinase structural genomics Thermotoga maritima TM1509 UPF0054 zinc-binding protein 

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Copyright information

© Springer 2005

Authors and Affiliations

  • Catherine Hervé du Penhoat
    • 1
    • 6
  • Zhaohui Li
    • 2
    • 6
  • Hanudatta S. Atreya
    • 1
    • 6
  • Seho Kim
    • 1
    • 6
    • 7
  • Adelinda Yee
    • 3
    • 4
    • 6
  • Rong Xiao
    • 5
    • 6
  • Diana Murray
    • 2
    • 6
  • Cheryl H. Arrowsmith
    • 3
    • 4
    • 6
  • Thomas Szyperski
    • 1
    • 6
    • 6
  1. 1.Department of ChemistryUniversity of Buffalo, The State University of New YorkBuffaloUSA
  2. 2.Department of Microbiology and Immunology and Institute for Computational BiomedicineB-314 Weill Medical College of Cornell UniversityNew YorkUSA
  3. 3.Division of Molecular and Structural BiologyOntario Cancer InstituteTorontoCanada
  4. 4.Department of Medical BiophysicsUniversity of TorontoTorontoCanada
  5. 5.Center for Advanced Biotechnology and Medicine and Department of Molecular Biology and BiochemistryRutgers UniversityPiscatawayUSA
  6. 6.Northeast Structural Genomics ConsortiumUSA
  7. 7.Chemistry DepartmentRutgers UniversityPiscatawayUSA

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