1999
DOI: 10.1073/pnas.96.16.8925
|View full text |Cite
|
Sign up to set email alerts
|

Abstract: Factor VIIa (EC 3.4.21.21) is a trypsin-like serine protease that plays a key role in the blood coagulation cascade. On injury, factor VIIa forms a complex with its allosteric regulator, tissue factor, and initiates blood clotting. More importantly, a surface-exposed ␣-helix in the protease domain (residues 307-312), which is located at the cofactor recognition site, is distorted in the free form of factor VIIa. This subtle structural difference sheds light on the mechanism of the dramatic tissue factor-induce… Show more

Help me understand this report

Search citation statements

Order By: Relevance

Paper Sections

Select...
1
1
1
1

Citation Types

3
123
1

Year Published

2000
2000
2011
2011

Publication Types

Select...
6
2

Relationship

1
7

Authors

Journals

citations
Cited by 148 publications
(127 citation statements)
references
References 35 publications
3
123
1
Order By: Relevance
“…Cysteine residues predicted to participate in disulfide bridges within the EGF domains (Cys-88-Cys-99, Cys site; and the sodium ion-binding motif Tyr-411 {225} (23). In contrast, the amino acid residues Ser-278-Glu-279-Thr-280-Ala-281-Asp-282 {96-100}, which contribute to the S2-S3 substratebinding pocket, are not conserved (24,25). Likewise, the flexible insertion loop Val-353-Ser-362 {170-178} implicated in the human factor VIIa-soluble tissue factor interaction is not conserved among the factor VII proteins and demonstrates a 5-aa deletion (between Thr-359 and Leu-360) in the zebrafish ( Fig.…”
Section: Resultsmentioning
confidence: 99%
See 1 more Smart Citation
“…Cysteine residues predicted to participate in disulfide bridges within the EGF domains (Cys-88-Cys-99, Cys site; and the sodium ion-binding motif Tyr-411 {225} (23). In contrast, the amino acid residues Ser-278-Glu-279-Thr-280-Ala-281-Asp-282 {96-100}, which contribute to the S2-S3 substratebinding pocket, are not conserved (24,25). Likewise, the flexible insertion loop Val-353-Ser-362 {170-178} implicated in the human factor VIIa-soluble tissue factor interaction is not conserved among the factor VII proteins and demonstrates a 5-aa deletion (between Thr-359 and Leu-360) in the zebrafish ( Fig.…”
Section: Resultsmentioning
confidence: 99%
“…In contrast, surface residues in the EGF-2͞SP contact region are poorly conserved, suggesting that the intermolecular interactions with human tissue factor are largely disrupted. This disruption includes the protease insertion loop Leu-371-Glu-385 {170-178}, which appears to undergo a conformational change between the bound and unbound structures of human factor VIIa (25). In the zebrafish protein, this loop demonstrates a 5-aa deletion and replacement of a neighboring conserved Met with Arg-348 {164}.…”
Section: Discussionmentioning
confidence: 99%
“…The TF⅐FVIIa complex initiates the coagulation reactions by activating its substrates factor X (FX), factor IX, and FVII. Recent insight into the structures of TF⅐FVIIa complex (26), FVIIa (27)(28)(29), and zymogen FVII (30) and advancements made in understanding the allosteric regulation of FVIIa (31,32) offer various strategies to inhibit enzyme activity. For instance, phage-displayed libraries of cyclic peptides yielded potent and specific peptides, such as E-76 (33), which binds to a FVIIa exosite (34).…”
mentioning
confidence: 99%
“…1). Crystal structures of FVIIa lacking its Gla domain show an extended conformation [2,3] similar to that observed for the full-length protein in complex with sTF [4]. Despite available structural data for FVIIa, the solution conformation of free full-length FVIIa is not clear, neither are the details of the structural changes in FVIIa upon Ca 2+ or sTF binding.…”
Section: Introductionmentioning
confidence: 58%
“…Thus, the fact that FVIIa does not need to undergo significant global conformational changes upon ligation will of course make its docking to the rigid sTF cofactor easier leading to increased affinity and stability. However, given the extended conformation of FVIIa bound to TF [4] and the existence of a hinge around residue 88 located between the two EGF-like domains [2], one would intuitively expect the average distance between the two probes attached to FVIIa in this study to be shorter in the absence of TF.…”
Section: Analysis Of Fret In Flexible Protein Structuresmentioning
confidence: 79%