Penhoat Catherine Hervé du, Li Zhaohui, Atreya Hanudatta S, Kim Seho, Yee Adelinda, Xiao Rong, Murray Diana, Arrowsmith Cheryl H, Szyperski Thomas
Department of Chemistry, University of Buffalo, The State University of New York, 816 Natural Sciences Complex, Buffalo, NY 14260, USA.
J Struct Funct Genomics. 2005;6(1):51-62. doi: 10.1007/s10969-005-5277-z.
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 alpha+beta fold comprising a four stranded beta-sheet with topology A( upward arrow), B( upward arrow), D( upward arrow), C( downward arrow) as well as five alpha-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 alpha-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.
150个氨基酸残基的蛋白质TM1509由海栖热袍菌（Thermotoga maritima）的YF09_THEMA基因编码。到目前为止，TM1509尚无功能注释，属于蛋白质家族UPF0054（PFAM登录号：PF02130），该家族至少包含146个成员。TM1509的核磁共振结构揭示了一种α+β折叠，包括一个具有A（向上箭头）、B（向上箭头）、D（向上箭头）、C（向下箭头）拓扑结构的四链β-折叠以及五个α-螺旋I-V。PF02130家族大多数成员的结构可以利用TM1509的核磁共振结构可靠地构建，这表明其在探索折叠空间方面具有很高的参考价值。TM1509与UPF0054家族同源物的多序列比对显示，三个多肽片段以及位于α-螺旋IV C末端的一个假定的锌结合共有基序HGXLHLXGYDH高度保守。这个UPF0054共有基序的三个组氨酸残基的空间排列类似于基质金属蛋白酶（MMPs）的HEXXHXXGXXH锌结合共有基序中组氨酸残基的排列。此外，其他保守的多肽片段形成一个大腔，包围着假定的锌结合口袋，并可能在催化过程中赋予特异性。然而，TM1509和UPF0054家族的其他成员在MMP共有基序的第2位没有关键的谷氨酸残基。有趣的是，TM1509的结构表明，UPF0054共有基序中的天冬氨酸（TM1509中的Asp 111）可能取代谷氨酸的催化作用。这表明蛋白质家族UPF0054可能包含一类迄今未被表征的金属蛋白酶成员。
